Laser systems and optical devices for manipulating laser beams

ABSTRACT

Various embodiments of a multi-laser system are disclosed. In some embodiments, the multi-laser system includes a plurality of lasers, a plurality of laser beams, a beam positioning system, a thermally stable enclosure, and a temperature controller. The thermally stable enclosure is substantially made of a material with high thermal conductivity such as at least 5 W/(m K). The thermally stable enclosure can help maintain alignment of the laser beams to a target object over a range of ambient temperatures. Various embodiments of an optical system for directing light for optical measurements such laser-induced fluorescence and spectroscopic analysis are disclosed. In some embodiments, the optical system includes a thermally conductive housing and a thermoelectric controller, a plurality of optical fibers, and one or more optical elements to direct light emitted by the optical fibers to illuminate a flow cell. The housing is configured to attach to a flow cell.

PRIORITY CLAIM

This application claims priority to U.S. Provisional Patent ApplicationNo. 62/133,241 entitled “Laser Systems and Optical Devices forManipulating Laser Beams” filed Mar. 13, 2015, which is incorporatedherein by reference in its entirety. This application also claimspriority to U.S. Provisional Patent Application No. 62/135,137 entitled“Laser Systems and Optical Devices for Manipulating Laser Beams” filedMar. 18, 2015, which is also incorporated herein by reference in itsentirety.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is related to a continuation-in-part, U.S. patentapplication Ser. No. 12/940,004, filed Nov. 4, 2010, titled “Compact,Thermally Stable Multi-Laser Engine”, which is a continuation-in-part ofU.S. patent application Ser. No. 12/418,537, filed Apr. 3, 2009, titled“Compact, Thermally Stable Multi-Laser Engine”, which claims the benefitof U.S. Provisional Application No. 61/042,652, filed Apr. 4, 2008, allof which are incorporated herein by reference in their entireties. Thisapplication is also related to another continuation-in-part, U.S. patentapplication Ser. No. 12/418,494, filed Apr. 3, 2009 and titled “Compact,Thermally Stable Fiber-Optic Array Mountable to Flow Cell”, which claimsthe benefit of U.S. Provisional Application No. 61/042,640, filed Apr.4, 2008, both of which are incorporated herein by reference in theirentireties. This application is also related to U.S. patent applicationSer. No. 14/103,709, filed Dec. 11, 2013, titled “Optical Systems”,which claims the benefit of U.S. Provisional Application No. 61/736,500,filed Dec. 12, 2012, both of which are incorporated herein by referencein their entireties. Accordingly, each of the above referencedapplications is incorporated herein by reference in their entireties.

BACKGROUND

Field

Part I

This disclosure generally relates to optical (e.g., fluorescent,spectroscopic) analysis of biological samples through flow cells and/oroptical fibers connected to confocal microscopes or “lab-on-a-chip”devices, and to, for example, compact, thermally stable multi-lasersystems configured to couple to flow cells, optical fibers, or othertarget objects and to provide illumination thereto.

Part II

This disclosure relates generally to optical systems for directing lightto a sample contained in a flow cell, and more particularly to acompact, thermally stable, optical fiber array attachable to a flow cellfor directing laser light to the flow cell for optical measurements suchas laser-induced fluorescence.

Description of Related Art

Part I

Optical analysis of flow cells, such as laser-induced fluorescence,involves illuminating biological samples with laser light in order totest samples which may, for example, be tagged with fluorescent dyes.Fluorescent dyes absorb light at certain wavelengths and in turn emittheir fluorescence energy at a different wavelength. This emission canbe detected to ascertain properties of the fluid in the flow cell.Existing systems for fluorescent analysis of flow cells, however, sufferfrom various drawbacks, such as measurement error.

Part II

Optical analysis of flow cells, such as laser-induced fluorescence,involves illuminating biological samples with laser light in order totest samples which may, for example, be tagged with fluorescent dyes.Fluorescent dyes absorb light at certain wavelengths and in turn emittheir fluorescence energy at a different wavelength. This emission canbe detected to ascertain properties of the fluid in the flow cell.Existing systems for fluorescent analysis of flow cells, however, sufferfrom various drawbacks, such as measurement error.

SUMMARY

Part I

Embodiments described herein have several features, no single one ofwhich is solely responsible for their desirable attributes. Withoutlimiting the scope of the invention as expressed by the claims, some ofthe advantageous features will now be discussed briefly.

Various embodiments described herein provide the ability to performoptical measurements on flow cells while addressing some of thedrawbacks encountered with conventional approaches, such as laser beamalignment to the flow cell that is sensitive to the ambient temperatureresulting in signal power fluctuations.

A wide range of embodiments are disclosed. Some embodiments, forexample, comprise a compact, thermally stable multi-laser system. Themulti-laser system comprises a plurality of lasers. The plurality oflasers outputs a plurality of respective laser beams. The system furthercomprises a beam positioning system. The beam positioning system isconfigured to position the plurality of laser beams closer together. Themulti-laser system further comprises beam focusing optics. The beamfocusing optics are configured to focus the plurality of laser beams.The multi-laser system further comprises a thermally stable enclosure.The thermally stable enclosure encloses the plurality of lasers, thebeam positioning system and the beam focusing optics. The thermallystable enclosure is configured to thermally and mechanically couple to aflow cell. The thermally stable enclosure substantially comprises amaterial with high thermal conductivity of at least 5 W/(m K). Thethermally stable enclosure has a volume of no more than 36 cubic inches.The system further comprises a temperature controller. The temperaturecontroller is configured to control the temperature of the thermallystable enclosure and to maintain the alignment of the focused laserbeams to the flow cell over a range of ambient temperatures.

In some embodiments, a compact, thermally stable multi-laser systemcomprises a plurality of lasers. The plurality of lasers outputs aplurality of respective laser beams. The system further comprises a beampositioning system. The beam positioning system is configured toreposition the plurality of laser beams. The system further comprises athermally stable enclosure. The thermally stable enclosure encloses theplurality of lasers and the beam positioning system. The thermallystable enclosure substantially comprises a material with high thermalconductivity of at least 5 W/(m K). The thermally stable enclosure isconfigured to control the temperature of the thermally stable enclosureand configured to maintain the alignment of the focused laser beams to atarget object over a range of ambient temperatures. The system furthercomprises a temperature controller. The temperature controller isconfigured to control the temperature of the thermally stable enclosure.Other embodiments are also disclosed.

Part II

Embodiments described herein have several features, no single one ofwhich is solely responsible for their desirable attributes. Withoutlimiting the scope of the invention as expressed by the claims, some ofthe advantageous features will now be discussed briefly.

Various embodiments described herein provide the ability to performoptical measurements on flow cells while addressing some of thedrawbacks encountered with conventional approaches, such as temperatureinstability and the resultant pointing errors and signal powerfluctuations. A wide range of embodiments, however, are disclosed.

Various embodiments disclosed herein, for example, comprise a lasersystem for directing light for optical measurements, such aslaser-induced fluorescence. The laser system can include a thermallyconductive housing defining an interior chamber, and a thermoelectriccontroller thermally coupled to the housing. The laser system caninclude a plurality of optical input ports, and the optical input portscan be configured to engage a plurality of input optical fibers andreceive light from the input optical fibers. The laser system caninclude a plurality of optical fibers contained within the interiorchamber, and the optical fibers can be configured to receive the lightfrom the optical input ports and output the light into the internalchamber. The laser system can include one or more optical elementsconfigured to receive the light output by the optical fibers and outputa plurality of beams of light. The laser system can include a flow cellconnector configured to attach a flow cell to the housing, and the flowcell connector can be configured to position the flow cell to intersectthe beams of light.

The thermoelectric controller can be configured to maintain the interiorchamber at a substantially constant temperature.

The plurality of beams of light produced by the one or more opticalelements can comprise a plurality of substantially elliptical beams oflight. The one or more optical elements can comprise a plurality ofanamorphic microlenses. The laser system can include one or more outputwindows, and the one or more output windows can be configured totransmit the beams of light out of the internal chamber.

The flow cell connector can be configured to attach the flow cell to theoutside of the housing. The housing can be hermetically sealed.

The plurality of input ports can be configured to removably engage theplurality of input optical fibers. The plurality of input ports cancomprise a plurality of FC connectors. The plurality of input ports cancomprise a plurality of angle-polished connections.

The plurality of optical fibers can comprise a plurality of input endsand a plurality of output ends, with the input ends being distributedacross a first distance and the output ends being distributed across asecond distance, wherein the first distance is greater than the seconddistance. Each output end can comprise a center, and the centers can bespaced about 110 to 140 micrometers apart. The one or more opticalelements can be configured to produce the beams of light spaced about110 to 140 micrometers apart. The centers can be spaced about 125micrometers apart, and the one or more optical elements can beconfigured to produce the beams of light spaced about 125 micrometersapart. The plurality of optical fibers can be polarization-maintainingoptical fibers.

The laser system of can include a plurality of input optical fiberscoupled to the optical input ports, and a plurality of laser lightsources coupled to the input optical fibers.

The laser system can include a flow cell attached to the housing via theflow cell connector, and the flow cell can be configured to direct asample fluid into the beams of light. The flow cell connector cancomprise thermally conducting material, and the flow cell connector canbe thermally coupled to the thermoelectric controller, and thethermoelectric controller can be configured to maintain the flow cell ata substantially constant temperature.

The one or more optical elements can be formed in the housing, the oneor more optical elements configured to transmit the light out of theinternal chamber, and the flow cell connector can be configured toattach the flow cell to the outside of the housing.

The flow cell connector can be configured to attach the flow cell to thehousing with the flow cell passing through the interior chamber, and theflow cell connector can comprise at least one seal configured to form aseal around the flow cell.

Various embodiments disclosed herein comprise a laser system fordirecting light for optical measurements. The laser system can include athermally conductive housing defining an interior chamber, and athermoelectric controller thermally coupled to the housing. The lasersystem can include a plurality of optical input ports, and the opticalinput ports can be configured to engage a plurality of input opticalfibers and receive light from the input optical fibers. The laser systemcan include a plurality of waveguides contained within the interiorchamber, and the waveguides can be configured to receive the light fromthe optical input ports and output the light into the internal chamber.The laser system can include one or more optical elements configured toreceive the light output by the waveguides and output a plurality ofbeams of light. The laser system can include a flow cell connectorconfigured to attach a flow cell to the housing, and the flow cellconnector can be configured to position the flow cell to intersect thebeams of light.

Various embodiments disclosed herein comprise a laser system fordirecting light for optical measurements. The laser system can include aplurality of optical fibers for receiving light from a plurality oflasers, and the optical fibers can have a plurality of output ends, andeach output end can include a center. The laser system can include anoptical fiber mount configured to orient the plurality of optical fiberswith the centers of said output ends spaced about 110 to 140 micronsapart. The laser system can include a flow cell connector configured toposition a flow cell forward the output ends. The optical fiber mountcan be configured to orient the plurality of optical fibers with thecenters of the output ends spaced about 125 microns apart.

Various embodiments disclosed herein comprise a laser system fordirecting light for optical measurements. The laser system can include aflow cell configured to provide a sample fluid for measurement, and aplurality of optical fibers for receiving light from a plurality oflasers. The optical fibers can have a plurality of output ends. Thelaser system can include an optical fiber mount configured to orient theplurality of optical fibers with the output ends positioned to emitlight toward said flow cell.

Various embodiments disclosed herein comprise a multi-laser system. Themulti-laser system can include a laser outputting a laser beam; and abeam adjusting system configured to adjust an angular position of thelaser beam and direct the adjusted laser beam toward a target object.The beam adjusting system comprises at least one meniscus shaped opticalelement having a first surface and a second opposite surface, where saidmeniscus shaped optical element is adjustable to adjust the angularposition of the laser beam.

Various embodiments disclosed herein comprise an optic system. The opticsystem includes a first lens for receiving a laser beam having aGaussian beam profile, said first lens configured to alter the beam sizeof the laser beam in at least one direction; a Powell lens configured toconvert said laser beam that has a Gaussian beam profile into a laserbeam having a flat top intensity distribution and an elongatedcross-section orthogonal to propagation of the beam, said elongatedcross-section having a length in a first direction that is longer thanin a second orthogonal direction; a second lens configured to collimatesaid laser beam at least in one direction; a translation stageconfigured to receive a control signal that drives movement of saidtranslation stage, where said Powell lens is coupled to the translationstage such that the Powell lens can be translated with respect to saidfirst and second lens in response to said control signal.

Various embodiments disclosed herein comprise an optic system foradjusting a translation stage with a coupled Powell lens. The opticsystem can include a translation stage configured to receive a voltage;a beam focusing optics unit comprising a first lens, a Powell lens,coupled to the translation stage, and a second lens; and a controlsystem including an image processing unit. The control system can beconfigured to adjust the translation stage by at least generating animage processing result representing an optical power distribution of abeam based on feedback corresponding to an optical image of a beamcross-section; determining, based on the image processing resultrepresenting the power distribution of the beam, to move a position ofthe translation stage; and sending, to the translation stage with thecoupled Powell lens, one or more signals to adjust the position of thetranslation stage in at least one coordinate plane. The feedback mayalso be a beam spot, an optical image of a cross-sectional shape, or across-section of a laser beam.

BRIEF DESCRIPTION OF THE DRAWINGS

The following drawings and the associated descriptions are provided toillustrate embodiments of the present disclosure and do not limit thescope of the claims.

FIG. 1 depicts an example embodiment of a multi-laser system.

FIG. 2 depicts another example embodiment of a multi-laser system.

FIG. 2A depicts another example embodiment of a multi-laser system inwhich the beam positioning/combining system comprises mirrors.

FIG. 2B depicts an example embodiment of a triangular prism.

FIG. 2C depicts an example embodiment of a rectangular prism.

FIG. 2D depicts an example embodiment of a multi-laser system includinga prism beam positioning/combining system.

FIG. 2E depicts an example embodiment of a prism beampositioning/combining system.

FIG. 3 depicts the front view of the system of FIG. 2.

FIG. 4 depicts the side view of the system of FIG. 2.

FIG. 5 depicts an example embodiment of a multi-laser system furtherincluding a plurality of beam adjusters.

FIG. 6 depicts an example embodiment of a multi-laser system furtherincluding focusing optics.

FIG. 7 depicts an example embodiment of a multi-laser system in whichthe beam adjusters comprise Risley prism pairs.

FIGS. 8A-8B depict example embodiments of a multi-laser system in whichthe beam adjusters comprise Risley prisms and plane parallel plates.

FIG. 9 depicts an example embodiment of a multi-laser system in whichthe target object comprises an optical fiber or waveguide.

FIG. 10 depicts an example embodiment of a multi-laser system in whichthe target object comprises an adjuster mount.

FIGS. 11A-11N depict example spatial arrangements of laser beams inmulti-laser systems.

FIG. 12 schematically shows an optical system that can be used to directlight to samples for performing optical measurements such aslaser-induced fluorescence and spectroscopic analysis.

FIG. 13 is a cross-sectional view of an embodiment of an optical fiberarray.

FIG. 14 schematically shows another optical system that can be used todirect light to samples for performing optical measurements such aslaser-induced fluorescence and spectroscopic analysis.

FIG. 15 schematically shows another optical system that can be used todirect light to samples for performing optical measurements such aslaser-induced fluorescence and spectroscopic analysis.

FIG. 16(a) illustrates an implementation of a multi-laser optical systemincluding a plurality of laser devices 101A, 101B, . . . , 101Nconfigured to emit light along a plurality of optical paths 102A, 102B,. . . , 102N respectively.

FIG. 16(b) illustrates an implementation of a meniscus shaped opticalelement 1605A including a first curved surface 1607 configured toreceive the incident laser beam and a second curved surface 1609opposite the first curved surface 1607 configured to output the laserbeam.

FIG. 16(c-1) depicts a laser beam with 0 degree boresight error that isincident on an implementation of an optical element 1605A.

FIG. 16(c-2) depicts a laser beam with about 1 degree boresight errorthat is incident on an implementation of an optical element 1605A.

FIG. 16(c-3) depicts a tilted configuration of the optical element tocorrect boresight error.

FIG. 16(d-1) illustrates the variation in the boresight angle changeexpressed in radians (rad) versus the change in the angle of incidence(AoI) which corresponds to the relative angle of incidence of the laserbeam with respect to the meniscus optical element expressed in degreesfor an implementation of a cylindrical meniscus shaped optical element.

FIG. 16(d-2) illustrates the variation in the boresight angle changeexpressed in milliradians (mrad) versus the change in the angle ofincidence (AoI) which corresponds to the relative angle of incidence ofthe laser beam with respect to the meniscus optical element expressed indegrees measured for an implementation of a cylindrical meniscus shapedoptical element.

FIG. 16(d-3) illustrates the measured variation in the boresight angleof an output laser beam expressed in milliradians (mrad) as a functionof tilt about the x-axis of an implementation of a spherical meniscusshaped optical element depicted by curve 1625.

FIG. 16(d-4) illustrates the measured variation in the boresight angleof an output laser beam expressed in milliradians (mrad) as a functionof tilt about the y-axis of an implementation of a spherical meniscusshaped optical element depicted by curve 1635.

FIG. 16(e-1) depicts a laser beam with about 0.5 degree boresight errorthat is incident on an implementation of an optical element 1605A.

FIG. 16(e-2) illustrates an implementation of a translated configurationof the optical element 1605A.

FIG. 17a depicts a laser system in which a Powell lens is used.

FIG. 17b depicts a laser system in which a Powell lens is used.

FIG. 18 illustrates an example method using a Powell lens in a lasersystem.

DETAILED DESCRIPTION

Part I

This application incorporates herein by reference in their entirety U.S.Patent Publication No. 2011/0134949 and corresponding U.S. patentapplication Ser. No. 12/940,004, filed Nov. 4, 2010, titled “Compact,Thermally Stable Multi-Laser Engine”, U.S. Patent Publication No.2009/0274176 and corresponding U.S. patent application Ser. No.12/418,537, filed Apr. 3, 2009, titled “Compact, Thermally StableMulti-Laser Engine”, as well as U.S. Provisional Application No.61/042,652, filed Apr. 4, 2008.

Although certain preferred embodiments and examples are disclosedherein, inventive subject matter extends beyond the specificallydisclosed embodiments to other alternative embodiments and/or uses ofthe inventions, and to modifications and equivalents thereof. Thus, thescope of the inventions herein disclosed is not limited by any of theparticular embodiments described below. For example, in any method orprocess disclosed herein, the acts or operations of the method orprocess may be performed in any suitable sequence and are notnecessarily limited to any particular disclosed sequence.

For purposes of contrasting various embodiments with the prior art,certain aspects and advantages of these embodiments are described. Notnecessarily all such aspects or advantages are achieved by anyparticular embodiment. Thus, for example, various embodiments may becarried out in a manner that achieves or optimizes one advantage orgroup of advantages as taught herein without necessarily achieving otheraspects or advantages as may also be taught or suggested herein.

FIG. 1 depicts an example embodiment of a multi-laser system. Themulti-laser system 100 depicted in FIG. 1 comprises a thermally stable,temperature controlled enclosure 150 configured to mechanically and/orthermally couple to a target object 1100. The enclosure 150 helps toisolate the laser and optics within the enclosure 150 from the ambientenvironment, which may have varying temperature. By maintaining thetemperature within the enclosure within a relatively small range,thermally induced laser wavelength and intensity fluctuations as well aspointing instabilities of the laser beams can be reduced or minimized.In some embodiments, the target object may comprise a flow cell, a flowcell mount, a light pipe, a waveguide, an optical fiber, or a lab on achip. In some embodiments, the target object may comprise a mountingmechanism, mounting system (e.g., mounting alignment system), etc. for aflow cell, a flow cell mount, a light pipe, a waveguide, an opticalfiber, and/or a lab on a chip.

In some embodiments, the temperature across the enclosure may be stableover time and with changes in the ambient temperature. The constanttemperature over time may help with long term system performance. Forexample if the enclosure temperature were to change with time, then thesystem performance would also potentially degrade with time. This couldeventually result in servicing the system, e.g., to realign the system.

The thermally stable enclosure 150 comprises a material with highthermal conductivity. In some embodiments, a material with thermalconductivity of at least about 5 W/(m K), (e.g., between about 5 W/(m K)and about 2000 W/(m K)) is used. In some embodiments, a material withthermal conductivity at least about 50 W/(m K) (e.g., between about 50W/(m K) and about 2000 W/(m K)) is used. In other embodiments, amaterial with thermal conductivity of about 375 W/(m K) or greater isused. In other embodiments, a material with thermal conductivity of atleast about 380 W/(m K) is used. In some embodiments, a material withthermal conductivity between about 125 W/(m K) and about 425 W/(m K)) isused. In some embodiments, a material with thermal conductivity betweenabout 375 W/(m K) and about 425 W/(m K)) is used. In some embodiments, amaterial with thermal conductivity between about 125 W/(m K) and about250 W/(m K)) is used. In some embodiments, a material with thermalconductivity between about 200 W/(m K) and about 250 W/(m K)) is used.In some embodiments, the material has a heat capacity corresponding othe heat capacity of the materials described herein. The use of suchthermally conductive material helps ensure a relatively reducedtemperature variation within the enclosure 150, even when the ambienttemperature outside of the enclosure varies relatively widely.

As described more fully below, a temperature controller in thermalcontact with the enclosure adjusts the temperature of the enclosure inresponse to variations in ambient conditions. A highly thermallyconductive enclosure enables the temperature controller to more quicklyand effectively maintain the enclosure and system temperature withouttemperature gradients in response to such variations in ambientconditions. A variety of thermally conductive materials can be used(e.g., copper, aluminum, copper tungsten, ceramics, epoxy, etc.). Insome embodiments, a material with a thermal conductivity of at least 5W/(m K) may be used. In other embodiments, a material with a thermalconductivity of less than 5 W/(m K) may be used. The thermallyconductive material can be used to form the entire enclosure, or merelya portion thereof. In certain embodiments, the enclosure substantiallycomprises highly thermally conductive material. For example, highlythermally conductive material can be used to form the top, the bottom,or any number of the sides of the enclosure 150, or any combinationthereof. In some embodiments, a majority of the enclosure 150 is made ofthe substantially thermally conductive material. In some embodiments,only a relatively small portion of the enclosure 150 is made of thethermally conductive material. In some embodiments, a substantialportion of the enclosure 150 is made of the substantially thermallyconductive material. In some embodiments, multiple substantiallythermally conductive materials can be used, with some areas of theenclosure 150 being more thermally conductive than others.

The multi-laser system 100 includes a plurality of lasers 101A-101N,enclosed within the thermally stable enclosure 150. The plurality oflasers 101A-101N may comprise diode lasers, solid-state lasers,frequency-doubled lasers, and/or other types of lasers. The plurality oflasers 101A-101N output a plurality of respective laser beams 102A-102N.Each of the laser beams 102A-102N may have a wavelength different fromthe other laser beams.

As shown in FIG. 1, the multi-laser system 100 further includes a beampositioning system 1000. To achieve a desired spatial arrangement of thelaser beams 102A-102N, the inherent laser beam boresight and centrationerrors present in lasers 101A-101N, as well angular and lateralpositioning errors present in the multi-laser system's opto-mechanicalcomponents can be compensated for. In some embodiments, the beampositioning/combining system 1000 may include mechanical and/oropto-mechanical provisions to perform such compensation.

Mechanical provisions to the laser mounting may be used to adjust theangular and/or lateral position of the lasers so that the boresight andcentration errors of the lasers 101A-101N as well as the angular andlateral positioning errors of the opto-mechanical components arecompensated for. The aligned laser beams may then be positioned orcombined by the beam positioning/combining system 1000 into a desiredspatial arrangement that a specific application requires.

Opto-mechanical provisions to the beam positioning/alignment system maybe used to allow for angular and lateral position adjustment of thelaser beams. This adjustment capability may help compensate for thelasers' boresight and centration errors as well as the angular andlateral positioning errors of the opto-mechanical components to achievea desired spatial arrangement of the laser beams.

In embodiments in which the system is used perform testing of biologicalsamples, flow cells are illuminated with laser beams. Fluorescent dyesabsorb light at certain wavelengths and in turn emit their fluorescenceenergy at a different wavelength. This emission can be detected toascertain properties of the fluid in the flow cell. Temperaturevariations may cause the wavelength and/or the intensity of light outputby the lasers to vary. Such variations in the laser beams directed intothe flow cell may cause fluctuations in output fluorescent signals,which may introduce inaccuracy in the optical measurements. Temperaturevariations and/or temperature gradients also may cause movement of theoptical elements (e.g., due to thermal expansion) and resultant shiftingof the laser beams. These pointing errors may cause the laser beams todeviate from the flow cell, such that the signal changes, or isaltogether lost, again introducing inaccuracy in the test results.

Temperature variations can result from ambient temperature fluctuations.Accordingly, reducing the temperature variation of and the presence oftemperature gradients within the laser beam system can improve theaccuracy and usability of the test results.

Various embodiments described herein may address one or more of theseproblems. FIG. 2 is a top view of another example embodiment of themulti-laser system 100. The multi-laser system 100 depicted in FIG. 2comprises a thermally stable enclosure 150 configured to mechanicallyand/or thermally couple to a flow cell 132. The thermally stableenclosure 150 helps to isolate the laser and optics within the enclosure150 from the ambient environment, which may have varying temperature. Insome embodiments, the enclosure 150 can achieve thermal stabilitythrough the use of a temperature controller, as discussed in relation toFIG. 3 below. In various embodiments, the enclosure 150 helps reducevariations in the temperature of the various components of themulti-laser system 100. By maintaining the temperature within theenclosure within a relatively small range, thermally induced laserwavelength and intensity fluctuations as well as pointing instabilitiesof the laser beams can be reduced or minimized and alignment of thelaser beams to a target object may be maintained over a range of ambienttemperatures (e.g., between about 10° C. and about 55° C.). Accordingly,the use of a thermally stable enclosure 150 may help achieve moreaccurate test results.

Some materials expand and contract when heated or cooled. Changes in theenclosure temperature or temperature variations across the enclosure canresult in a change in the relative positions of lasers, mirrors, lenses,and the target object (e.g., flow cell). Some lasers exhibit beampointing that is temperature dependent. This may be due in part to thefact that different materials are used in the construction of the laser(e.g., metals, glass, adhesives, etc). The different materials may havedifferent thermal expansion coefficients, which may cause beamdeviations when the laser system's temperature changes. Some mirror andlens systems also show some temperature dependence for the same reason.

The multi-laser system 100 depicted in FIG. 2 includes a plurality oflasers 101, 102, 103 enclosed within the thermally stable enclosure 150.Although FIG. 2 includes three lasers, a different number of lasers canbe used. The multi-laser system 100 shown in FIG. 2 includes a 405 nmlaser, a 488 nm laser and a 635 nm laser, but other wavelengths can alsobe used (e.g., lasers having wavelengths of 375 nm, 440 nm, 515 nm, 561nm, 594 nm, 640 nm, etc.).

The plurality of lasers 101, 102, 103 output a plurality of respectivelaser beams 104, 105, 106. Laser beam 104 has a first wavelength, laserbeam 105 has a second wavelength, and laser beam 106 has a thirdwavelength. The first, second, and third wavelengths are different fromone another. In FIG. 2, these wavelengths are 405 nm, 488 nm and 635 nm,respectively, but other wavelengths can also be used (e.g., 375 nm, 440nm, 515 nm, 561 nm, 594 nm, 640 nm, etc.).

As shown in the example embodiment of FIG. 2, the multi-laser system 100further includes a plurality of automatic power control (APC) modules107, 108, 109. In some embodiments, the APC modules 107, 108, 109 mayeach comprise a beamsplitter (not shown) and a photodetector (not shown)configured to sample light from the laser beams 104, 105, 106,respectively, and to feed back the signal from the detector incommunication with a laser controller (not shown) to adjust the outputpower of lasers 101, 102, 103, respectively. Other approaches may alsobe possible.

Referring still to FIG. 2, the beam positioning system comprises aplurality of wavelength selective mirrors 110, 111, 112, 113. In variousembodiments, some of the wavelength selective 110, 111, 112, 113 mirrorshave significantly different reflection or transmission properties atdifferent wavelengths. Accordingly, the wavelength selective mirrors110, 111, 112, 113 can separate or combine laser beams with differentwavelengths. In some embodiments, the mirrors 110, 112 may be broadband,for example because light is not transmitted through the mirrors 110,112. Through the use of suitable optical coatings, wavelength selectivemirrors exhibit high reflection over some range of wavelengths and hightransmission over another range of wavelengths. The wavelength selectivemirrors are appropriate for the wavelengths of the laser sources. Forexample, various of the wavelength selective mirrors will selectivelyreflect (or transmit) light propagating from one laser at a firstwavelength and not light propagating from another laser at a secondwavelength. The example embodiment of FIG. 2 depicts four wavelengthselective mirrors 110, 111, 112, 113. In other embodiments, a differentnumber of wavelength selective mirrors may be used (e.g., see FIG. 2A).In some embodiments, the wavelength selective mirrors may comprisedichroic and trichroic mirrors. Dichroic mirrors can separate or combinelasers with two different wavelengths. In various embodiments dichroicmirrors may allow at least one wavelength to substantially or totallypass through and may substantially or totally reflect at least onewavelength. Trichroic mirrors can separate or combine lasers with threedifferent wavelengths. Trichroic mirrors may be optimized for threewavelengths, they may have three peaks or one broad peak that coversmultiple wavelengths. In other embodiments, the wavelength selectivemirrors may comprise mirrors with selectivity for a different number ofwavelengths. Alternatively, substantially non-wavelength selectivemirrors that do not selectively reflect (or transmit) light of one laserand not light of another laser may be inserted in the path of the beamto redirect and/or alter the beam path or the beam. Other opticalelements can be inserted into the optical path.

The wavelength selective mirrors 110, 111, 112, 113 are configured withhighly reflective and anti-reflective coatings in accordance with thewavelengths of the plurality of laser beams 104, 105, 106. As shown inFIG. 2, wavelength selective mirror 110 is configured to be highlyreflective of the wavelength of the laser beam 104 (e.g., 405 nm, allwavelengths); wavelength selective mirror 111 is configured to be highlyreflective of the wavelength of the laser beam 104 (e.g., 405 nm) andanti-reflective of the wavelength of the laser beam 105 (e.g., 488 nm);wavelength selective mirror 112 is configured to be highly reflective ofthe wavelength of the laser beam 106 (e.g., 635 nm, all wavelengths),and wavelength selective mirror 113 is configured to be highlyreflective of the wavelength of the laser beam 106 (e.g., 635 nm), andanti-reflective of the wavelengths of the laser beams 104 (e.g., 405 nm)and 105 (e.g., 488 nm). In other embodiments, the wavelength selectivemirrors can be configured to be highly reflective of some wavelengthsand anti-reflective of some other wavelengths in order to separate orcombine the wavelengths as necessary.

In some embodiments, this plurality of wavelength selective mirrors 110,111, 112, 113 may be supported by a plurality of respective flexuremounts (not shown). Flexure mounts are less likely to move with externalvibrations and thus are less likely to require adjustment. Flexuremounts reduce impact on the optics from shocks such as may be introducedby shipping of the system. Additionally, flexure mounts typicallyexhibit less hysteresis than rolling or sliding contacts. Flexure mountsare typically fabricated from materials which make them relatively lesssensitive to temperature variations. Flexure mounts may also be smallerthan conventional spring loaded mounts. In some embodiments, the flexuremounts may comprise a nickel-iron alloy material for example. Othermaterials may also be used. In other embodiments, the plurality ofwavelength selective mirrors 110, 111, 112, 113 may be supported by aplurality of respective spring-loaded mirror mounts (not shown). Inother embodiments, the plurality of wavelength selective mirrors 110,111, 112, 113 may be supported by a plurality of respective glue-blockmounts (not shown).

In the multi-laser system 100 shown in FIG. 2, three optical paths aredepicted. A first optical path at a wavelength of 405 nm originates atlaser 101, passes through the APC 107, where a portion of the signal ispicked off (e.g., by a beam splitter), is then highly reflected atwavelength selective mirrors 110 and 111 and transmitted throughwavelength selective mirror 113, and then arrives at the focusing optics117. A second optical path at a wavelength of 488 nm originates at laser102, passes through the APC 108, where a portion of the signal is pickedoff (e.g., by a beam splitter), is then transmitted through wavelengthselective mirrors 111 and 113, and then arrives at the focusing optics117. A third optical path at a wavelength of 635 nm originates at laser103, passes through the APC 109, where a portion of the signal is pickedoff (e.g., by a beam splitter), is then reflected at wavelengthselective mirrors 112 and 113, and then arrives at the focusing optics117. Propagating along these paths, laser beams 104, 105, 106, which mayhave originally been far from one another, are repositioned to be closertogether as beams 114, 115, 116 and, after the focusing optics, beams118, 119, 120, respectively. In some embodiments, the beams 118, 119,120 are parallel to one another. In other embodiments, the beams 118,119, 120 are not parallel to one another. Other mirrors and opticalcomponents (e.g., lenses, prisms, polarization rotators, waveplates,etc.) can be included to alter the laser beams and/or optical paths.

Still referring to FIG. 2, the multi-laser system 100 further includesoptional beam focusing optics 117 to provide size reduction and/orshaping to the output laser beams 118, 119, 120. For example, thefocusing optics 117 may focus a laser beam down to a smaller spot.Additionally, the focusing optics 117 may change the shape of the laserbeams. In some embodiments, for example, the laser beams 118, 119, 120can have a generally Gaussian profile, so that when illuminating a flowcell, the intensity of the light illuminating the center of the flowcell is significantly greater than the intensity of the lightilluminating the peripheral edges of the flow cell. Accordingly, thebeams of light 118, 119, 120 can be elongated (e.g., elliptical) beams,so that the relatively high intensity center regions of the light beamsextend across the entire width of the flow cell, while the relativelylow intensity outer regions of the light beams do not strike the flowcell. By using an elongated (e.g., elliptical) beam of light, a moreuniform distribution of light across the width of the flow cell or othertarget output can be achieved while illuminating a relatively smalllongitudinal area along the length of the flow cell and maintainingsubstantially uniform high light intensity.

In some embodiments, the beams 114, 115, 116 enter the beam focusingoptics 117 and can have circular cross-sections with a Gaussianfall-off. In some embodiments, the beam focusing optics 117 may includean anamorphic lens system which may produce non-rotationally symmetricor elongated beam such as a beam with elliptical cross-section and spotsize. In other embodiments, the beam focusing optics 117 may includecylindrical lenses. In some embodiments, the beam focusing optics 117may include spherical lenses. In some embodiment, the beam focusingoptics 117 may include powell lenses (Gaussian to flat-toptransformers). In some embodiments, the beam focusing optics 117 mayinclude aspherical lenses. The focusing optics may be achromatic withreduced chromatic aberration thereby reducing positioning error whichmay otherwise result from different color laser beams. Accordingly,achromatic anamorphic optics, achromatic elliptical optics, achromaticspherical optics and achromatic aspherical optics, may be used. In someembodiments, lenses can be an anamorphic microlens array. In someembodiments, refractive and/or diffractive optics can be used to producethe elongated beams of light 118, 119, 120. Other types of optics arepossible.

In cases where the laser comprises a semiconductor laser, the laser beamoutput may already be elliptical-shaped, and optics to convert theelliptical beam into a circular beam can be substantially excluded. Insuch cases, there would be no need to include anamorphic focusing opticsto make the elliptical-shaped beam spherical (e.g., rotationallysymmetric). Spherical or rotationally symmetric optics may be employedwithout anamorphic elements.

The output laser beams 118, 119 and 120 depicted in FIG. 2 may haverespective spot sizes of between about 55 μm and about 110 μm in onedirection and between about 5 μm and about 15 μm in another direction(e.g., perpendicular to the one direction). In other embodiments, thelaser beams may have respective spot sizes of between about 70 μm andabout 110 μm in one direction and between about 5 μm and about 15 μm inanother direction (e.g., perpendicular to the one direction). In otherembodiments, the laser beams may have respective spot sizes of betweenabout 50 μm and about 150 μm in one direction and between about 5 μm andabout 20 μm in another direction (e.g., perpendicular to the onedirection). In other embodiments, the laser beams may have spot sizes ofbetween about 55 μm and about 100 μm in one direction and between about5 μm and about 15 μm in another direction (e.g., perpendicular to theone direction). In other embodiments, the laser beams may have spotsizes of between about 70 μm and about 100 μm in one direction andbetween about 5 μm and about 15 μm in another direction (e.g.,perpendicular to the one direction). In other embodiments, the laserbeams may have respective spot sizes of between about 50 μm and about150 μm in one direction and between about 5 μm and about 20 μm inanother direction (e.g., perpendicular to the one direction). In someembodiments, the output laser beams 118, 119, 120 may have respectivespot sizes of about 80 μm in one direction and about 10 μm in anotherdirection (e.g., perpendicular to the one direction). In otherembodiments, the output laser beams 118, 119, 120 may have respectivespot sizes of about 100 μm in one direction and about 10 μm in anotherdirection (e.g., perpendicular to the one direction). The directions maycorrespond to major and minor axes of an ellipse for a beam with anelliptical cross-section and spot shape. Other sizes and shapes arepossible for the light beams.

Still referring to FIG. 2, the multi-laser system 100 includes couplingto a flow cell 132. The multi-laser system 100 can include an outputwindow 121 that allows the beams of light 118, 119, 120 to exit theenclosure 150. The output window 121 can be made from, for example,fused silica, glass, acrylic, or a variety of other transparentmaterials (e.g., plastic). In some embodiments, the enclosure 150includes an aperture 122 in a wall thereof and the output window 121comprises a transparent window pane 124 positioned over the aperture122. The window pane 124 can be made from, for example, fused silica,glass, acrylic, or a variety of other transparent materials (e.g.,plastic). The aperture 122 and window pane 124 can assume a variety ofshapes, but in some embodiments they are rectangular, circular, orelliptical. The window 121 can be attached to the enclosure 150 by aplurality of fasteners such as bolts 126. In FIG. 2, only two bolts 126are shown, but in some embodiments, additional bolts can be positionedalong the edges of the window 121. In some embodiments, the window 121can include a flange for mounting the window. The flange may have aplurality of through holes through which fasteners (e.g., bolts 126) canpass to secure the window 121 to the enclosure 150. A seal 128 (e.g., anO-ring) can be positioned between the enclosure 150 and the window 121.The bolts 126 can be tightened, causing the O-ring 128 to be compressedbetween the enclosure 150 and the window 121. In some embodiments, theO-ring 128 produces a hermetic seal. Other approaches can be used tofasten the window 121 to the enclosure 150. The window 121 can besecured to the enclosure 150 by an adhesive, epoxy, or cement.

In some embodiments, the seal described may produce a hermetic seal. Ahermetic seal may help reduce particles and contamination from outsidethe enclosure. A hermetic seal may also help to prevent or reduce theflow of air currents and thus prevent or reduce the flow of ambienttemperature changes into the enclosure. This in turn may help reducetemperature instability within the enclosure. In some of the embodimentsdiscussed above, the entire enclosure 150 is hermetically sealed fromthe ambient air. Thus, the interior of the enclosure 150 is isolatedfrom air currents which can cause temperature variation, and theinternal optical elements are protected from external contaminants. Insome embodiments a getter (not shown) is located inside the enclosure150 which can reduce contaminant particles or chemical species.Additional, a desiccant (not shown) can be positioned inside theenclosure 150 to reduce moisture.

Although FIG. 2 shows a single output window, multiple output windowscan be used. For example, each beam of light 118, 119, 120 can exit theenclosure 150 via a respective output window. In some embodiments, it isdesirable that as much as possible of the enclosure 150 comprise thethermally conductive material, to better achieve temperature uniformity.Accordingly, the output windows can be separated by thermally conductivematerial and can cover only as much area as necessary to allow lightbeams 118, 119, 120 to leave the enclosure 150. However, in someembodiments, a single output window is easier and less expensive toconstruct.

The multi-laser system 100 can include a flow cell connector (not shown)that is mechanically and thermally coupled to the enclosure 150, and theflow cell connector is configured to secure a flow cell 132 so that itintersects and maintains the alignment of the beams of light 118, 119,120. In some embodiments, the flow cell connector can permanently attachthe flow cell 132 to the enclosure 150. However, in some embodiments,the flow cell connector can allow the flow cell 132 to be removablyattached to the enclosure 150. In some embodiments, the flow cellconnector can be compatible with multiple types and/or sizes of flowcells. For example, the flow cell connector can include a clip, afriction or pressure fit coupling, a threaded portion configured toreceive a corresponding threaded portion of the flow cell 132, or avariety of other connectors known in the art or yet to be devised. Theflow cell 132 can be a capillary flow cell, and at least part of theflow cell can comprise a transparent material (e.g., fused silica orglass) that allows the light beams 118, 119, 120 to enter the flow cell132 and interact with a sample fluid contained within the flow cell 132.The flow cell 132 can be a thin hollow tube, forming a flow path thathas a diameter of about 10 μm. Other flow cell types and/or sizes can beused, and the flow cell 132 can be oriented differently than as shown inFIG. 1. In some embodiments, the beams of light 118, 119, 120 strike theflow cell over areas centered about 110 μm to about 140 μm apart fromeach other, and in some embodiments, about 125 μm apart from each other.In some embodiments, the beams of light 118, 119, 120 strike the flowcell over areas centered about 100 μm to about 150 μm apart from eachother. In some embodiments, the beams of light 118, 119, 120 strike theflow cell over areas centered about 100 μm to about 500 μm apart fromeach other. In some embodiments, the beams of light 118, 119, 120 strikethe flow cell over areas centered up to about 500 μm apart from eachother. In some embodiments, the thermal expansion coefficient of thethermally stable enclosure 150 matches the thermal expansion coefficientof the flow cell 132. Matching of thermal expansion coefficients mayhelp reduce overall stress on the flow cell. For some forms of opticalmeasurements, it may be desirable for the different laser beams to befocused to different locations in the flow cell 132 at specificlocations (e.g., areas spaced about 125 μm apart).

FIG. 2A depicts another example embodiment of a multi-laser system inwhich the beam positioning/combining system comprises mirrors. As shownin FIG. 2A, a beam positioning combiner system that employs mirrorsmounted onto a frame may be used. In various embodiments, the frames onwhich the mirrors are mountable may be adjustable, e.g., translatable,tiltable, etc. In various embodiments, the wavelength selective mirrorshave significantly different reflection or transmission properties atdifferent wavelengths. Accordingly, the wavelength selective mirrors canseparate or combine laser beams with different wavelengths.

Through the use of suitable optical coatings, wavelength selectivemirrors will selectively reflect (or transmit) light of at least onewavelength and not light of at least one other wavelength. In otherembodiments, the wavelength selective mirrors may comprise mirrors withselectivity for a different number of wavelengths. The exampleembodiment of FIG. 2A depicts a plurality of wavelength-selectivemirrors. The mirrors can be used to separate or combine lasers withdifferent wavelengths. Alternatively, substantially non-wavelengthselective mirrors that do not selectively reflect (or transmit) light ofone laser and not light of another laser may be inserted in the path ofthe beam to redirect and/or alter the beam path or the beam. Otheroptical elements can also be inserted into the optical path.

The wavelength-selective mirrors 221A, 221B . . . 221N are configuredwith highly reflective and anti-reflective coatings in accordance withthe wavelengths of the plurality of laser beams 102A, 102B . . . 102N.As shown in FIG. 2A, wavelength selective mirror 221A is configured tobe highly reflective of the wavelength of the laser beams 102B through102N and anti-reflective of the wavelength of laser beam 102A;wavelength-selective mirror 221B is configured to be highly reflectiveof the wavelength of the laser beam 102B and anti-reflective of thewavelength of the laser beam 102N; and wavelength selective mirror 221Nis configured to be highly reflective of the wavelength of the laserbeam 102N. Other configurations are possible.

In the multi-laser system 100 shown in FIG. 2A, a plurality of opticalpaths are depicted. A first optical path originates at laser 101A and istransmitted through wavelength selective mirror 221A and transmittedtoward the target object 1100. A second optical path originates at laser101B, is then reflected at wavelength selective mirrors 221B and 221A,and transmitted toward the target object 1100. An n-th optical pathoriginates at laser 101N, is then reflected at wavelength selectivemirror 221N, transmitted at wavelength selective mirror 221B, reflectedat wavelength selective mirror 221A, and transmitted toward the targetobject 1100. Propagating along these paths, laser beams 102A-102N, whichmay have originally been far from one another, are repositioned to becloser together as beams 2001A-2001N.

The mirrors may be configured to adjust the position of the plurality oflaser beams to be at a certain distance of one another, for example inaddition to the spacing adjustment that may be provided by placing thelasers at different heights within the enclosure. In some embodiments,the laser beams can be positioned to be coaxial, slightly offset butparallel to each other, or slightly offset but not parallel to eachother.

FIG. 2B depicts an embodiment of a triangular prism. The prism is atransparent optical element comprising a substantially transparentoptical material. The prism has flat, polished surfaces that reflectand/or refract light. One or more of these surfaces may be coated withan optical coating such as an interference coating that is reflectiveand/or anti-reflective. In some embodiments the coating is wavelengthselective. For example, the prism may be configured to be highlyreflective for certain wavelengths (e.g., of a first laser), and highlyanti-reflective for other wavelengths (e.g., of a second laser). Theexact angles between the surfaces depend on the application. As shown,the triangular prism generally has a triangular base and rectangularsides. Prisms may be made out of glass, or any material that istransparent to the wavelengths for which they are designed. In someembodiments, the material may include one of polymer, polycarbonate,polyethylene terephthalate, glycol-modified polyethylene terephthalate,amorphous thermoplastic, and/or other substrates. Prisms can be used toreflect light, and to split light into components with different, e.g.,wavelength, polarizations. As illustrated in FIG. 2B, a triangular prismincludes a glass surface configured to allow transmission of a laserbeam of a given wavelength. The surface may be coated with a reflectivecoating to allow for the reflection of the laser beam of a differentwavelength. In some embodiments, each of the wavelength selectivemirrors illustrated in FIGS. 2 and 2A may be replaced with a triangularprism as the one illustrated in FIG. 2B. Triangular prisms may also beused that reflect a plurality of wavelength, for example, using totalinternal reflection. Accordingly, the prisms may be used to redirectlaser beams and not for wavelength selection in various cases.

FIG. 2C depicts an embodiment of a rectangular prism. This rectangularprism comprises two triangular prisms contacted together. As illustratedin FIG. 2C, a rectangular prism may be used to deflect a beam of light,for example, by 90 degrees, although other angles are also possible. Asdescribed above, in some embodiments, prisms employ total internalreflection at the surfaces rather than for dispersion. If light insidethe prism hits one of the surfaces at a sufficiently steep angle(greater than the critical angle), total internal reflection occurs andall of the light is reflected. This makes a prism a useful substitutefor a mirror in some situations. As described above, triangular prismsor prisms having other shapes can also be used for this purpose. In someembodiments, rectangular prisms can be wavelength selective. Forexample, the interface between the two triangular prisms or prismportions that make up the rectangular prism shown in FIG. 2C can includean optical coating such as an interference coating that is wavelengthselective. In some embodiments, for example, the rectangular prismselectively reflects one laser wavelength and selectively transmitsanother wavelength. Accordingly, the rectangular prism may include oneor more coatings that are highly reflective for one or more laserwavelength. The rectangular prism may include one or more coatings thatare anti-reflective for one or more laser wavelength. In someembodiments, each of the wavelength selective mirrors illustrated inFIGS. 2 and 2A may be replaced with a rectangular prism such as the oneillustrated in FIG. 2C. Other arrangements and configurations are alsopossible. For example, a prism (e.g., a rectangular prism) may comprisetwo or more triangular or other shape prisms that are contactedtogether.

FIG. 2D depicts an embodiment of the multi-laser system including aprism or prism bar beam positioning/combining system 1000C. As shown inFIG. 2D, a prism-based beam positioning combiner system is used to allowthe lasers to be arranged in a row at one end of the temperaturecontrolled enclosure. In some embodiments, the prism beampositioning/combining system may include optically contacted prismshaving one or more surfaces coated to allow for the selectivetransmission or reflection of the laser beams. By proper selection ofthe surface coatings (such as for example wavelength selectivereflective interference coatings), various lasers of differentwavelength may be combined and output from the prism beampositioning/combining system. The prism beam positioning/combiningsystem may also be configured and arranged with respect to the lasersand the respective laser beam paths such that the laser beams can bepositioned such that they are, for example, closely spaced and/orparallel or co-linear on the output side of the prism-based beampositioning combiner system. In other embodiments, the prism beampositioning/combining system can be configured to position the beams inconverging or diverging with respect to one another.

The prism illustrated in FIG. 2D may comprise a plurality of prisms orprism portions contacted or adhered together (e.g., using opticalcontact bonding, or optical adhesive at optical interfaces, and thelike) to make a monolithic multi-prism beam combiner, or an aggregatedprism. In some embodiments, a monolithic multi-prism may comprise 2, 3,4, 5, or more prism portions. For example, a monolithic multi-prism maycomprise N+1 or N+2 prism portions, where N is the number of lasers. Insome embodiments, a monolithic multi-prism may comprise 1, 2, 3, 4, ormore optical interfaces. For example, a monolithic prism may comprise Nor N+1 optical interfaces, where N is the number of lasers. In variousembodiments, one or more interface between the prism portions may bewavelength selective. For example, various of the prism portions may beconfigured to have one ore more wavelength selective surfaces with oneor more highly reflective and/or an anti-reflective (e.g., interference)coatings in accordance with the wavelengths of the plurality of laserbeams 102A-102N. As shown in FIG. 2D, the wavelength selective internalsurface 3001A may be configured to be highly anti-reflective of thewavelength of the laser beam 102A and highly reflective of thewavelengths of laser beams 102B-102N. The wavelength selective internalsurface 3001B may be configured to be highly reflective of thewavelength of the laser beam 102B. The wavelength selective surfaceinternal surface 3001N may be configured to be highly reflective of thewavelength of the laser beam 102N.

In the embodiment shown in FIG. 2D, various prisms are contactedtogether (e.g., using cement, adhesive (e.g., optical adhesive), opticalcontact bonding) to form a monolithic multi-prism beam combiner or anintegrated or aggregated prism in the shape of a rectangular structureor bar having a rectangular base and rectangular sides. The differentprisms that are contacted together may have different shapes. Some ofthe prisms, for example, may have a base in the shape of a parallelogramand rectangular sides. Some of the other prisms may have differentshaped bases and rectangular sides. For example, at least one triangularprism is shown. Other shapes and configurations are also possible.

In the multi-laser system 100 shown in FIG. 2D, a plurality of opticalpaths are depicted. A first optical path originates at laser 101A, istransmitted through a prism portion to the internal surface 3001A, andthen is transmitted toward the target object 1100. A second optical pathoriginates at laser 101B, then is reflected at internal surfaces 3001Aand 3001B, and then is transmitted toward the target object 1100. Ann-th optical path originates at laser 101N, is transmitted throughinternal surfaces 101B through 101N-1, then is reflected at internalsurface 3001A, and then is transmitted toward the target object 1100.Propagating along these paths, laser beams 102A-102N, which may haveoriginally been far from one another, are repositioned to be closertogether as beams 3201A-3201N.

The prisms and interfaces therebetween within the prism-based beampositioning/combining system are configured to adjust the position ofthe plurality of laser beams to be at a certain distance from oneanother, in addition to the spacing adjustment that may be provided byplacing the lasers at different heights within the enclosure. In someembodiments, the laser beams can be positioned to be coaxial, slightlyoffset but parallel to each other, or slightly offset but not parallelto each other.

FIG. 2E depicts another embodiment of a prism beam positioning/combiningsystem. As shown in FIG. 2E, a prism-based beam positioning combinersystem is used to allow the lasers to be spread out over the surface ofthe temperature controlled enclosure's base plate. The surfaces of theprisms may be coated to allow for the transmission or reflection of thelaser beams. The prism illustrated in FIG. 2E may comprise a pluralityof prisms or prism portions contacted or adhered together to make anaggregated prism or a monolithic multi-prism beam combiner. In variousembodiments, one or more interface between the prism portions may bewavelength selective. For example, various of the prism portions may beconfigured to have one ore more wavelength selective surfaces with oneor more highly reflective and/or an anti-reflective (e.g., interference)coatings in accordance with the wavelengths of the plurality of laserbeams 102A-102N. As shown in FIG. 2E, the wavelength selective internalsurface 3601A may be configured to be highly anti-reflective of thewavelength of the laser beam 102A and highly reflective of thewavelength of laser beam 102B. The wavelength selective internal surface3601B may be configured to be highly anti-reflective of the wavelengthof the laser beams 102A and 102B and highly reflective of the wavelengthof laser beam 102C. The wavelength selective surface internal surface3601C may be configured to be highly anti-reflective of the wavelengthof the laser beams 102A, 102B, and 102C, and highly reflective of thewavelength of the laser beam 102D. The wavelength selective surfaceinternal surface 3601N may be configured to be highly anti-reflective ofthe wavelength of the laser beams 102A, 102B, 102C, through 102N-1, andhighly reflective of the wavelength of the laser beam 102N.

In the embodiment shown in FIG. 2E, various prisms are contactedtogether (e.g., using cement, adhesive (e.g., optical adhesive), opticalcontact bonding) to form an integrated or aggregated prism in the shapeof a rectangular structure or bar having a rectangular base andrectangular sides, or a monolithic multi-prism beam combiner. Thedifferent prisms that are contacted together have different shapes. Forexample, different triangular prisms are shown. Some of the prisms, forexample, may have a base in the shape of a right angle triangle andrectangular sides while other prisms may have a base in the shape of anequilateral triangle and have rectangular sides. Other shapes andconfigurations are also possible.

In the multi-laser system 100 shown in FIG. 2E, a plurality of opticalpaths are depicted. A first optical path originates at laser 101A, istransmitted through prism portions and internal surfaces 3601A, 3601B,3601C through 3601N, and is transmitted toward the target object 1100. Asecond optical path originates at laser 101B, is then reflected atinternal surface 3601A, transmitted through prism portions and internalsurfaces 3601B, 3601C through 3601N, and toward the target object 1100.A third optical path originates at laser 101C, is then reflected atinternal surface 3601B, transmitted through prism portions and internalsurfaces 3601C through 3601N, and toward the target object 1100. Afourth optical path originates at laser 101D, is reflected at internalsurface 3601C, transmitted through prism portions and internal surfaces3601D through 3601N, and toward the target object 1100. An n-th opticalpath originates at laser 101N, is reflected at internal surface 3601N,and transmitted toward the target object 1100. Propagating along thesepaths, laser beams 102A-102N, which may have originally been coming fromdifferent directions and far from one another, are repositioned to becloser together as beams 3701A-3701N. As described herein, the laserbeams 102A-102N may also be repositioned to be parallel to each other asbeams 3701A-3701N.

A wide range of other aggregated prisms (or monolithic multi-prism beamcombiners) comprising a plurality of prism portions contacted togetherare also possible. Aggregated prisms (or monolithic multi-prism beamcombiners) may include optical coating for example at interfaces betweenprism portions or prisms that make up the aggregated prism. Theseoptical coatings may be wavelength selective reflective coating or maybe anti-reflective (AR) coatings. One example of such an aggregatedprism comprising a plurality or prisms or prism portions contactedtogether is the X-prism. Other aggregated prisms, however, may also beused.

A multi-prism beam combiner may be more advantageous than beam combinersusing separate dichroic mirrors mounted in individual flexure mounts,mounted using a glue-block approach, or all mounted in a common mount.In a multi-prism beam combiner, all of the reflective surfaces are tiedtogether so that the number of opto-mechanical components that cancontribute to the relative movement of the laser beams with respect toeach other is greatly reduced thereby improving the system performance.Additionally, the reduced parts count and reduced complexity make forincreased ease of manufacturing and should allow for a decrease insystem size. Furthermore, the number of surfaces exposed to possiblecontamination is reduced. Also, the relatively large size of the prismcombiner compared to an individual dichroic mirror reduces the impactthat the coefficient of thermal expansion (CTE) mismatch between mostadhesives, the optics and the metal used in the optical mounts has onbeam position.

FIG. 3 depicts the front view of the multi-laser system 100 depicted inFIG. 2. As described above, in some embodiments, the thermally stableenclosure 250 is hermetically sealed. The hermetic sealing may beprovided by o-rings 233. Again, hermetically sealing can reduceparticles and contamination from outside the enclosure. Moreover, asdescribed above, a hermetic seal may also reduce or prevent the flow ofair currents and thus prevent or reduce the flow of ambient temperaturechanges into the enclosure. This in turn may reduce temperatureinstability within the enclosure. In some embodiments, the top ofenclosure 250 may be thermally coupled, possibly with a copper braid, tothe main body of the enclosure 250 to reduce thermal effects.

As shown in FIG. 3, the multi-laser system may further comprise atemperature controller 252. In some embodiments, the temperaturecontroller 252 may comprise a thermo electric cooler (TEC), atemperature sensor and control electronics. The TEC may pump heat fromone side to the other depending on the direction of current flow throughthe TEC. The direction of current flow may be determined by the controlelectronics. In some embodiments, for example, if the ambienttemperature were higher than the enclosure 250's set point temperaturethen the control electronics may direct current flow through the TEC sothat heat was pumped out of the enclosure 250 thereby helping maintainthe enclosure's set point temperature. In other embodiments, if theambient temperature were lower than the enclosure 250's set pointtemperature, then the control electronics may reverse the current flowthrough the TEC so that heat was pumped into the enclosure 250 againhelping maintain the enclosure's set point temperature. A temperaturecontroller 252 can be thermally coupled to the thermally stableenclosure 250. The temperature controller 252 can include a temperaturesensor (not shown) to measure the temperature of the thermally stableenclosure 250, and to provide feedback to the control electronics. Insome embodiments, the temperature sensor may comprise a thermistor. Thetemperature controller 252 may remove heat from or add heat to thethermally stable enclosure 250 in order to maintain a substantiallyconstant temperature in the thermally stable enclosure 250. The highthermal conductivity of the material of the enclosure 250 helps thetemperature controller to relatively quickly adjust the temperaturewithin the enclosure 250 in response to temperature variations outsideof the enclosure 250 and also reduce the presence of temperaturevariations across the enclosure 250.

As shown in FIG. 3, the multi-laser system may also comprise a baseplate260. The baseplate 260 may act as a thermal heat sink for thetemperature controller 252.

In some embodiments, the temperature within the thermally stableenclosure 250 can be held stable to within ±1° C., ±2° C., ±3° C., ±5°C., etc., for example, of a target temperature. In some embodiments, thetemperatures of the wavelength selective mirrors and the focusing opticscan be held to be within ±1° C., ±2° C., ±3° C., ±5° C., etc. of oneanother. In some embodiments, the temperature over a substantial portionof the enclosure can be held to be within ±1° C., ±2° C., ±3° C., ±5°C., etc. In some embodiments, the temperature over the entire enclosurecan be held to be within ±1° C., ±2° C., ±3° C., ±5° C., etc., forexample, of a target temperature. In some embodiments, the temperaturewithin the enclosure can be held to be within ±1° C., ±2° C., ±3° C.,±5° C., etc., for example, of a target temperature. In some embodiments,the temperature within the thermally stable enclosure 250 can be heldwithin ±1° C. of the target temperature. In some embodiments, the targettemperature can be between 10° C. and 50° C. In some embodiments, thetarget temperature can be between about 15° C. and about 45° C. In otherembodiments, the target temperature can be between about 15° C. andabout 35° C. In other embodiments, the target temperature can be betweenabout 10° C. and about 40° C. The temperature controller 252 alsomaintains the focused laser beams aligned with respect to the flow cellover a wide range of ambient temperatures. In some embodiments, therange of ambient temperatures can be between about 10° C. and about 55°C. In some embodiments, the range of ambient temperatures can be betweenabout 10° C. and about 50° C. In some embodiments, the range of ambienttemperatures can be between about 15° C. and about 45° C. In otherembodiments, the range of ambient temperatures can be between about 15°C. and about 35° C. In other embodiments, the range of ambienttemperatures can be between about 10° C. and about 40° C.

FIG. 3 also depicts that the three lasers 201, 202, and 203 may beplaced at different heights within the enclosure 250. The placement atdifferent heights may assist in positioning the focused laser beams at adesired spacing from one another at the flow cell. By disposing thelasers at different heights, the focused beams at the flow cell may beseparated by between about 110 μm and about 140 μm of one another. Insome embodiments, the focused beams may be separated by between about100 μm to about 150 μm of one another. In some embodiments, the focusedbeams may be separated by between about 100 μm to about 500 μm of oneanother. In some embodiments, the focused beams may be separated by upto about 500 μm of one another. The wavelength selective mirrors,however, can additionally be adjusted to account for the imperfection inlaser positions that may result, for example, from manufacturingtolerances. Accordingly, the wavelength selective mirrors may establishbetter positioning of the beams directed onto the flow cell.

FIG. 4 depicts the side view of the multi-laser system 100 depicted inFIG. 2. FIG. 4 also shows the placement of the lasers at differentheights. The thermally stable enclosure 350 comprises wavelengthselective mirrors 310, 311, 312, 313 that are configured to adjust theposition of the plurality of laser beams 314, 315, 316 to be at acertain distance of one another, in addition to the spacing adjustmentthat may be provided by placing the lasers at different heights withinthe enclosure 350. In some embodiments, the laser beams can bepositioned to be coaxial, slightly offset but parallel to each other, orslightly offset but not parallel to each other. In some embodiments, theplurality of focused laser beams 318, 319, 320 may be separated by about110 μm and about 140 μm of one another. In some embodiments, theplurality of focused laser beams 318, 319, 320 may be separated by about100 μm and about 150 μm of one another. In some embodiments, theplurality of focused laser beams 318, 319, 320 may be separated by about100 μm and about 500 μm of one another. In some embodiments, theplurality of focused laser beams 318, 319, 320 may be separated by up toabout 500 μm of one another. In some embodiments, the plurality offocused laser beams 318, 319, 320 may be positioned to be at a distanceof about 125 μm of one another.

As can be seen in FIG. 4, the thermally stable enclosure 350 comprises atop, a bottom, and four sides. In some embodiments, the thermally stableenclosure 350 has a width of about 3 inches or less, a length of about 6inches or less, and/or a height of about 2 inches or less. In otherembodiments, the length, the width, and the height of the thermallystable enclosure 350 may be relatively larger or smaller. In someembodiments, the thermally stable enclosure 350 has a width of about 6inches or less, a length of about 12 inches or less, and/or a height ofabout 3 inches or less. In some embodiments, the thermally stableenclosure 350 has a volume of 36 cubic inches (in³) or less. With arelatively small volume, the temperature controller is better able toadjust the temperature of the enclosure and system in response tovariations in ambient temperature. The temperature controller is thusable to avoid temporal variations in temperature induced by fluctuationin ambient conditions. The relatively small volume may reducetemperature instabilities within the enclosure 350 by reducingtemperature gradients across the enclosure 350. In other embodiments,the volume of the thermally stable enclosure 350 may be relativelylarger or smaller. Also shown in FIG. 4 is the flow cell connection 330,described above.

FIG. 5 depicts an example embodiment of a multi-laser system furtherincluding an optional plurality of beam adjusters 504A-504N. In variousembodiments, the boresight and centration errors of the n laser beamsand/or the angular and lateral positioning errors of the opto-mechanicalcomponents may be compensated for by using the separate beam positionadjusters 504A-504N. The adjusted laser beams may then be positionedand/or combined into a desired spatial arrangement by the beampositioning/combining system that a specific application requires.

FIG. 6 depicts the embodiment of the multi-laser system of FIG. 5further including optional focusing or beam shaping optics 117. Asdescribed in relation to FIG. 2 above, beam focusing optics or beamshaping optics may be used to provide size reduction and/or shaping tothe output laser beams. For example, the focusing/beam shaping opticsmay focus a laser beam down to a smaller spot. The focusing/beam shapingoptics may also be used to change the shape of the laser beams.

The output laser beams depicted in FIG. 6 may have respective spot sizesof between about 55 μm and about 110 μm in one direction and betweenabout 5 μm and about 15 μm in another direction (e.g., perpendicular tothe one direction). In other embodiments, the laser beams may haverespective spot sizes of between about 70 μm and about 110 μm in onedirection and between about 5 μm and about 15 μm in another direction(e.g., perpendicular to the one direction). In other embodiments, thelaser beams may have respective spot sizes of between about 50 μm andabout 150 μm in one direction and between about 5 μm and about 20 μm inanother direction (e.g., perpendicular to the one direction). In otherembodiments, the laser beams may have spot sizes of between about 55 μmand about 100 μm in one direction and between about 5 μm and about 15 μmin another direction (e.g., perpendicular to the one direction). Inother embodiments, the laser beams may have spot sizes of between about70 μm and about 100 μm in one direction and between about 5 μm and about15 μm in another direction (e.g., perpendicular to the one direction).In other embodiments, the laser beams may have respective spot sizes ofbetween about 50 μm and about 150 μm in one direction and between about5 μm and about 20 μm in another direction (e.g., perpendicular to theone direction). In some embodiments, the output laser beams 118, 119,120 may have respective spot sizes of about 80 μm in one direction andabout 10 μm in another direction (e.g., perpendicular to the onedirection). In other embodiments, the output laser beams 118, 119, 120may have respective spot sizes of about 100 μm in one direction andabout 10 μm in another direction (e.g., perpendicular to the onedirection). These may correspond to major and minor axes of an ellipsefor a beam with an elliptical cross-section and spot shape. Other sizesand shapes are possible for the light beams.

FIG. 7 depicts an example embodiment of a multi-laser system in whichthe beam adjusters 504A-504N comprise Risley prism pairs 705A-705N. Inother embodiments, other systems may be used as the separate beamposition adjusters 504A-504N. In various embodiments, the laserboresight and opto-mechanical angular errors may be compensated for byrotating the Risley prisms while the laser centration andopto-mechanical lateral positioning errors may be compensated for byadjusting the Risley prism assembly pitch, yaw, and/or separationbetween the individual prisms (e.g., by adjusting one or both of theindividual prisms). The aligned laser beams may then be positioned orcombined into a desired spatial arrangement that a specific applicationrequires by the beam positioning/combining system.

FIG. 7 depicts a Risley prism pair used with each laser beam. In otherembodiments, a different number of Risley prisms may be used. Otheroptical elements can also be inserted into the optical path.

In various embodiments, Risley prisms comprising wedged optics, usuallyused in pairs, to redirect optical beams are used. In variousembodiments, an incoming light beam enters a Risley prism pair,experiences refraction and redirection under Snell's Law, and exits theRisley prism pair. In some configuration of the Risley prisms, there isjust a translation of the output beam with respect to the input beam. Ifthe arrangement of the Risley prisms with respect to each other ischanges, the output beam may experience an elevation deviation. Theability to control azimuth may be provided by rotating the prism pairtogether. Therefore, the Risley prism pair can be used to direct a lightbeam at a variety of elevation angles and azimuthal angles.

The Risley prism pairs 705A-705N wedge angles and the azimuthal rotationbetween the prisms are determined in accordance with the respectivelaser beam 102A-102N. As shown in FIG. 6, Risley prism pair 705A isconfigured to adjust the laser beam 102A, Risley prism pair 705B isconfigured to adjust the laser beam 102B, and Risley prism pair 705N isconfigured to adjust the laser beam 102N.

In the multi-laser system 100 shown in FIG. 7, a plurality of opticalpaths are depicted. A first optical path originates at laser 101A,passes through the Risley prism pair 705A, where laser boresight,centration and opto-mechanical angular and lateral positioning errorsmay be compensated through adjustment of the wedge angles of and theazimuthal rotation between the prism pair 705A, and then arrives at thebeam combining/positioning system 1000. A second optical path originatesat laser 101B, passes through the Risley prism pair 705B, where laserboresight, centration and opto-mechanical angular and lateralpositioning errors may be compensated through adjustment of the wedgeangles of and the azmiuthal rotation between the prism pair 705B, andthen arrives at the beam combining/positioning system 1000. An N-thoptical path originates at laser 101N, passes through the Risley prismpair 705N, where laser boresight, centration and opto-mechanical angularand lateral positioning errors may be compensated through adjustment ofthe wedge angles of and the azimuthal rotation between the prism pair705N, and then arrives at the beam combining/positioning system 1000.

Propagating along these paths, laser beams 102A-102N, which may haveoriginally been far from one another, are repositioned to be closertogether as beams 1001A-1001N. In some embodiments, the beams1001A-1001N are parallel to one another. In other embodiments, the beams1001A-1001N are not parallel to one another. Other optical components(e.g., lenses, prisms, polarization rotators, waveplates, etc.) can beincluded to alter the laser beams and/or optical paths.

FIGS. 8A-8B depict example embodiments of a multi-laser system in whichthe beam adjusters comprise Risley prisms and plane parallel plates. Inthe embodiment of FIG. 8A, a combination of Risley prism pairs 705A-705Nand glass etalon plates 707A-707N are used for the separate beamposition adjusters 504A-504N illustrated in FIG. 5. In otherembodiments, the etalon plates may be comprised of material other thanglass. In some embodiments, the plane parallel plates may be made out ofglass, or any material that is transparent to the wavelengths for whichthey are designed. In some embodiments, the material may include one ofpolymer, polycarbonate, polyethylene terephthalate, glycol-modifiedpolyethylene terephthalate, amorphous thermoplastic, and/or othersubstrates. The etalon plates comprise plane parallel plates. Otheroptical elements may however be used in different embodiments.Adjustment of the beams may be provided for by using the combination ofRisley prism pairs as described in relation to FIG. 7 above, and glassetalon plates 707A-707N. In the embodiment of FIG. 8A, a single glassetalon plate may be used for providing correction to lateral positioningerrors in both x and y planes. In the embodiment of FIG. 8B, a separateglass etalon plate is used for correcting later positioning errors ineach (e.g., by being tiltable along one axis) of the x and y planes orin both (e.g., by being tiltable along multiple axes) of the x and yplanes.

In various embodiments, the laser boresight and opto-mechanical angularerrors may be compensated for by rotating the prisms while the lasercentration and opto-mechanical lateral positioning errors may becompensated for by adjusting the pitch and/or yaw of the paralleloptical plate. The aligned laser beams may then be positioned orcombined into a desired spatial arrangement by the beampositioning/combining system that a specific application requires.

In the multi-laser system 100 shown in FIG. 8A, a plurality of opticalpaths are depicted. A first optical path originates at laser 101A,passes through the Risley prism pair 705A, where laser boresight andopto-mechanical angular errors may be compensated through adjustment ofthe wedge angles of the prism pair 705A, passes through the glass etalonplate 707A, where laser centration and opto-mechanical lateralpositioning errors may be compensated for by adjusting the pitch and/oryaw of the glass etalon plate 707A, and then arrives at the beamcombining/positioning system 1000. A second optical path originates atlaser 101B, passes through the Risley prism pair 705B, where laserboresight and opto-mechanical angular errors may be compensated throughadjustment of the wedge angles of the prism pair 705B, passes throughthe glass etalon plate 707B, where laser centration and opto-mechanicallateral positioning errors may be compensated for by adjusting the pitchand/or yaw of the glass etalon plate 707B, and then arrives at the beamcombining/positioning system 1000. An N-th optical path originates atlaser 101N, passes through the Risley prism pair 705N, where laserboresight, and opto-mechanical angular errors may be compensated throughadjustment of the wedge angles of the prism pair 705N, passes throughthe glass etalon plate 707N, where laser centration and opto-mechanicallateral positioning errors may be compensated for by adjusting the pitchand/or yaw of the glass etalon plate 707N, and then arrives at the beamcombining/positioning system 1000.

In the multi-laser system 100 shown in FIG. 8B, a plurality of opticalpaths are depicted. A first optical path originates at laser 101A,passes through the Risley prism pair 705A, where laser boresight andopto-mechanical angular errors may be compensated through adjustment ofthe wedge angles of the prism pair 705A, passes through glass etalonplates 707A, 708A, where laser centration and opto-mechanical lateralpositioning errors may be compensated for by adjusting the pitch and/oryaw of the glass etalon plates 707A and/or 708A, and then arrives at thebeam combining/positioning system 1000. A second optical path originatesat laser 101B, passes through the Risley prism pair 705B, where laserboresight and opto-mechanical angular errors may be compensated throughadjustment of the wedge angles of the prism pair 705B, passes throughglass etalon plates 707B, 708B, where laser centration andopto-mechanical lateral positioning errors may be compensated for byadjusting the pitch and/or yaw of the glass etalon plates 707B and/or708B, and then arrives at the beam combining/positioning system 1000. AnN-th optical path originates at laser 101N, passes through the Risleyprism pair 705N, where laser boresight, and opto-mechanical angularerrors may be compensated through adjustment of the wedge angles of theprism pair 705N, passes through glass etalon plates 707N, 708N, wherelaser centration and opto-mechanical lateral positioning errors may becompensated for by adjusting the pitch and/or yaw of the glass etalonplates 707N and/or 708N, and then arrives at the beamcombining/positioning system 1000.

Propagating along these paths, laser beams 102A-102N, which may haveoriginally been far from one another, are repositioned to be closertogether as beams 1001A-1001N. In some embodiments, the beams1001A-1001N are parallel to one another. In other embodiments, the beams1001A-1001N are not parallel to one another. Other optical components(e.g., lenses, prisms, polarization rotators, waveplates, etc.) can beincluded to alter the laser beams and/or optical paths.

FIG. 9 depicts an example embodiment of a multi-laser system in whichthe target object 1100 comprises an optical fiber or waveguide. Anoptional lens 902 may be used to couple the beams into the optical fiber900. As shown in FIG. 9, the n laser beams may be combined, for example,by one of the embodiments for beam positioning and combining describedabove, or any combination of the embodiments described above and coupledinto an optical fiber or waveguide. Both the coupling optics and fiberor waveguide may be located inside the temperature controlled enclosureand hard-mounted to the enclosure's temperature controlled base plate901.

FIG. 10 depicts an example embodiment of a multi-laser system in whichthe target object 1100 comprises an adjuster mount 1010. This adjustermount may be configured to receive an optical fiber 900. Fiber opticcoupling mounts are commercially available. In various embodiments, thefiber optic coupling mounts may comprise coupling optics mounted onefocal length away from the optical fiber input with the optical axis ofthe coupling optics co-linear with a beam that would be emitted from theoptical fiber. The coupling optics and optical fiber are mounted in ametal housing (e.g., a cylindrical housing) so that the alignmentbetween the coupling optics and optical fiber input is maintained. Thiscomponent may be a coupler/collimator assembly. In some embodiments, themounts may comprise coupling optics and fiber in a metal housing. Thecoupler/collimator assembly is inserted into a positioning mount whichis attached to the temperature controlled enclosure. For polarizationmaintaining fibers the coupler/collimator assembly and positioningmounts may be keyed so as to provide registration between thepolarization axis of the laser beams and the polarization axis of theoptical fiber. The positioning mount may be made of metal. The mount hasmechanical adjusters that allow the pitch, yaw and lateral position ofthe coupler/collimator assembly to be moved relative to the input laserbeams to optimize the amount of light coupled into the optical fiber. Asshown in FIG. 10, the n laser beams may be combined, for example, by oneof the embodiments for beam positioning and combining described above,or any combination of the embodiments described above and coupled intothe adjustor mount or an optical element such as an optical fibercoupled to the adjuster mount. The optical fiber, coupling optics andcoupling optimization hardware may be mounted at least partially on theoutside of the temperature controlled enclosure.

FIGS. 11A-11N depict example types and spatial arrangements of laserbeams in multi-laser systems. The specific desired type and spatialarrangement of the laser beams may be application specific. The laserbeams themselves may be collimated or focused. In some applications,however, it may be desirable to focus the laser beam in order to createsmall spot sizes at the target object and, hence, to increase powerdensity or brightness on the target object. Accordingly, laser beamsthat are collimated or focused beams may be used. A plurality ofcollimated or a plurality of focused beams may be substantiallyco-linear to one another at the target object. The plurality of beamsmay alternatively be substantially parallel to one another but spacedapart from each other, or converging towards each other, or divergingaway from one another at the target object. In some embodiments, theplurality of parallel beams may have identical beam separations (such asa substantially constant separation d₀) at the target object, ordifferent beam separations (such as separations d₁, d₂, . . . ) at thetarget object. In some embodiments, the plurality of converging ordiverging beams may have identical angular separations (such as asubstantially constant separation θ₀) at the target object, or differentangular separations (such as separations θ₁, θ₂, . . . ) at the targetobject. In some embodiments, the angular separation may be less thanabout 5°.

Some example spatial arrangements of laser beams are depicted in FIGS.11A-11N.

FIG. 11A depicts parallel collimated beams with identical beamseparations, d₀.

FIG. 11B depicts parallel collimated beams with different beamseparations, d₁ and d₂.

FIG. 11C depicts converging collimated beams with identical angularseparations, θ₀.

FIG. 11D depicts converging collimated beams with different angularseparations, θ₁ and θ₂.

FIG. 11E depicts diverging collimated beams with identical angularseparations, θ₀.

FIG. 11F depicts diverging collimated beams with different angularseparations, θ₁ and θ₂.

FIG. 11G depicts co-linear collimated beams.

FIG. 11H depicts parallel focused beams with identical beam separations,d₀.

FIG. 11I depicts parallel focused beams with different beam separations,d₁ and d₂.

FIG. 11J depicts converging focused beams with identical angularseparations, θ₀.

FIG. 11K depicts converging focused beams with different angularseparations, θ₁ and θ₂.

FIG. 11L depicts diverging focused beams with identical angularseparations, θ₀.

FIG. 11M depicts diverging focused beams with different angularseparations, θ₁ and θ₂.

FIG. 11N depicts co-linear focused beams.

Configurations other than those described herein are possible. Thestructures, devices, systems, and methods may include additionalcomponents, features, and steps and any of these components, features,and steps may be excluded and may or may not be replaced with others.The arrangements may be different. Reference throughout thisspecification to “some embodiments,” “certain embodiments,” or “anembodiment” means that a particular feature, structure or characteristicdescribed in connection with the embodiment is included in at least someembodiments. Thus, appearances of the phrases “in some embodiments” or“in an embodiment” in various places throughout this specification arenot necessarily all referring to the same embodiment and may refer toone or more of the same or different embodiments. Furthermore, theparticular features, structures or characteristics may be combined inany suitable manner, as would be apparent to one of ordinary skill inthe art from this disclosure, in one or more embodiments.

As used in this application, the terms “comprising,” “including,”“having,” and the like are synonymous and are used inclusively, in anopen-ended fashion, and do not exclude additional elements, features,acts, operations, and so forth. Also, the term “or” is used in itsinclusive sense (and not in its exclusive sense) so that when used, forexample, to connect a list of elements, the term “or” means one, some,or all of the elements in the list.

Similarly, it should be appreciated that in the above description ofembodiments, various features are sometimes grouped together in a singleembodiment, figure, or description thereof for the purpose ofstreamlining the disclosure and aiding in the understanding of one ormore of the various inventive aspects. This method of disclosure,however, is not to be interpreted as reflecting an intention that anyclaim require more features than are expressly recited in that claim.Rather, inventive aspects lie in a combination of fewer than allfeatures of any single foregoing disclosed embodiment.

Although the inventions presented herein have been disclosed in thecontext of certain preferred embodiments and examples, it will beunderstood by those skilled in the art that the inventions extend beyondthe specifically disclosed embodiments to other alternative embodimentsand/or uses of the inventions and obvious modifications and equivalentsthereof. Thus, it is intended that the scope of the inventions hereindisclosed should not be limited by the particular embodiments describedabove.

Part II

This application incorporates herein by reference in their entirety U.S.Patent Application Publication 2009/0257054 and corresponding U.S.patent application Ser. No. 12/418,494, filed Apr. 3, 2009 and titled“Compact, Thermally Stable Fiber-Optic Array Mountable to Flow Cell”, aswell as U.S. Provisional Application No. 61/042,640, filed Apr. 4, 2008.

Embodiments of the inventions will now be described with reference tothe accompanying figures. Although certain preferred embodiments andexamples are disclosed herein, inventive subject matter extends beyondthe specifically disclosed embodiments to other alternative embodimentsand/or uses of the inventions, and to modifications and equivalentsthereof. Thus, the scope of the inventions herein disclosed is notlimited by any of the particular embodiments described below. Forexample, in any method or process disclosed herein, the acts oroperations of the method or process may be performed in any suitablesequence and are not necessarily limited to any particular disclosedsequence.

For purposes of contrasting various embodiments with the prior art,certain aspects and advantages of these embodiments are described. Notnecessarily all such aspects or advantages are achieved by anyparticular embodiment. Thus, for example, various embodiments may becarried out in a manner that achieves or optimizes one advantage orgroup of advantages as taught herein without necessarily achieving otheraspects or advantages as may also be taught or suggested herein.

FIG. 12 schematically shows an optical system 5100 that can be used todirect light to a sample for performing optical measurements such aslaser-induce fluorescence and spectroscopic analysis. The optical system5100 can include a housing 5102 enclosing an interior chamber 5104. Thehousing 5102 can be made of a thermally conductive material. Thethermally conductive material can have a thermal conductivity betweenabout 50 W/(m-K) and about 2000 W/(m-K). For example, the thermallyconductive material may be copper which has a thermal conductivity ofabout 380 W/(m-K). A variety of thermally conductive metals can be used(e.g., copper or aluminum), as well as thermally conductive non-metals(e.g., ceramics or epoxy). The thermally conductive material can be usedto form the entire housing, or merely a portion thereof. For example,substantially thermally conductive material can be used to form the top,the bottom, or any number of the sides of the housing 5102, or anycombination thereof. In some embodiments, a majority of the housing 5102is made of the substantially thermally conductive material. In someembodiments, only a relatively small portion of the housing 5102 is madeof the substantially thermally conductive material. In some embodiments,a substantial portion of the housing 5102 is made of the substantiallythermally conductive material. In some embodiments, multiplesubstantially thermally conductive materials can be used, with someareas of the housing 5102 being more thermally conductive than others.

In some of the embodiments discussed above, the housing is hermeticallysealed from the ambient air. Thus, the interior chamber 5104 is isolatedfrom air currents which can cause temperature variation, and theinternal optical elements are protected from external contaminants. Insome embodiments a getter (not shown) is located inside interior chamber5104 which can reduce contaminant particles or chemical species.Additional, a desiccant (not shown) can be positioned inside theinterior chamber 5104 to reduce moisture.

A thermoelectric controller 5106 can be thermally coupled to the housing5102. The thermoelectric controller 5106 can include one or moretemperature sensors (not shown) (e.g., thermistors) to measure thetemperature of the housing 5102 and/or the temperature of the interiorchamber 5104, and a heat transfer system (not shown) for removing heatfrom or adding heat to the housing 5102 in order to maintain asubstantially constant temperature in the housing or in the interiorchamber. In some embodiments, the thermoelectric controller 5106 caninclude a cooler for removing heat (e.g., heat resulting from operationof the optical system). In some embodiments, the thermoelectriccontroller 106 can include a heater for heating the housing 5102 andinternal chamber 5104. In some embodiments, the heater can be used tomaintain the internal chamber 5104 at a temperature above theanticipated highest ambient temperature. In some embodiments, thethermoelectric controller 5106 can include a thermoelectric cooler(TEC). The heat transfer system can be coupled directly to the housing5102 and to the cooler and/or heater (e.g. TEC). In some embodiments,the temperature can be held within held within ±1° C., ±2° C., ±3° C.,±5° C., etc. of the target temperature. In some embodiments, thetemperature of the interior chamber 5104 is between 15° C. and 45° C.

In some embodiments, the housing is compact. For example, the housingmay be a size of less than 10 cubic inches. The relatively small size ofthe volume allows for rapid adjustment of temperature in response tovariations in the ambient temperature and thus more precise control ofthe temperature in the internal chamber 5104.

The optical system 5100 can include a number of optical input ports5108A-5108D. Although the embodiment shown in FIG. 12 includes fouroptical input ports, a different number of optical input ports can beused. In some embodiments, the optical input ports 5108A-5108D can besecured and hermetically sealed into respective apertures formed in thehousing 5102, and can engage optical fibers 5110A-5110D. A variety offiber connectors can be used, such as screw-type optical fiberconnectors (e.g., an FC connector), snap-type fiber connectors, or otherfiber connectors known in the art or yet to be devised. In someembodiments, the optical input ports 5108A-5108D include anangle-polished fiber connector (e.g., an FC/APC connector). In someembodiments, at least a portion of the optical input ports 5108A-5108D,such as the threading of a screw-type connector, can be integrallyformed as part of the housing 5102. The optical fibers 5110A-5110Dinclude fiber connectors (not shown) configured to securely andprecisely mate with the optical input ports 5108A-5108D so that lightcan be efficiently transferred from the optical fibers 5110A-5110D to aplurality of optical fibers 5114A-5114D within the internal chamber5104. In some embodiments, the optical fibers 5110A-5110D are singlemode optical fibers. Highly polarized light can be injected into theoptical fibers 5110A-5110D (e.g., from a diode laser), and in someapplications it can be advantageous to preserve the polarization of thelight. Accordingly, polarization-maintaining optical fibers can be used.In some embodiments different types of optical fibers can be connectedto different optical input ports 5108A-5108D. Likewise, in someembodiments, the different optical input ports 5108A-5108D can comprisedifferent types of optical connectors.

The optical fibers 5110A-5110D can be coupled to laser light sources5112A-5112D. Although the embodiment shown in FIG. 12 includes fourlasers, a different number of lasers can be used. The lasers 5112A-5112Dcan include a variety of different laser types and can provide light ofvariety of different wavelengths. The optical system 5100 shown in FIG.12 includes a 405 nm laser, a 488 nm laser, a 561 nm laser, and a 640 nmlaser, but other common wavelengths of laser light can be used (e.g.,light having a wavelength of 440 nm, 635 nm, or 375 nm). The lasers5112A-5112D can be diode lasers, diode-pumped solid state lasers,frequency doubled lasers, or other laser types that produce light usefulfor example in laser-induced fluorescence and spectroscopic analysis.Although FIG. 12 shows the lasers 5112A-5112D connected to the opticalinput ports 5108A-5108D via the optical fibers 5110A-5110D, in someembodiments the optical fibers 5110A-5110D and the lasers 5112A-5112Dcan be disconnected from the optical input ports 5108A-5108D by the userso that other lasers can be interchangeably connected to the opticalsystem 5100. Thus, the optical system 5100 is a versatile tool which auser can easily modify to utilize a wide variety of lasers withoutdifficult and time consuming adjustments.

The optical system 5100 can include a plurality of optical fibers5114A-5114D contained within the internal chamber 5104. The opticalfibers 5114A-5114D can be optically coupled to the optical input ports5108A-5108D so that they receive light from the optical input ports5108A-5108D and direct the light into the internal chamber 5104. In someembodiments, the cores of the optical fibers 5114A-5114D can be exposedby optical input ports 5108A-5108D so that the cores of the opticalfibers 5110A-5110D can contact the cores of the optical fibers5114A-5114D directly or come in substantial proximity to the cores ofoptical fibers 5114A-5114D. As with the optical fibers 5110A-5110Ddiscussed above, the optical fibers 5114A-5114D can be single modeoptical fibers and can be polarization-maintaining optical fibers.

In some embodiments, the optical system can include a fiber supportstructure 5116 that is configured to change the pitch of the opticalfibers 5114A-5114D, bringing the output ends closer together than theinput ends. For example, the optical input ports 5108A-5108D can bespaced about 10 to 20 millimeters or more apart from each other, so thatthe user can conveniently connect and disconnect optical fibers. Theinput ends of the optical fibers 5114A-5114D, which are coupled to theoptical input ports 5108A-5108D, can be similarly distributed forexample about 10 to 20 millimeters or more apart. The fiber supportstructure 5116 can have grooves (e.g., V-grooves) defining generallyconverging pathways, and the optical fibers 5114A-5114D can be securedin the grooves by a top-plate positioned over the grooves or by anadhesive. In some embodiments, the V-grooves can be configured toprecisely hold the fibers. In some embodiments, silicon V-groovesmanufactured using silicon processing techniques (e.g., etching,photoresists, etc.) can be used to secure the optical fibers5114A-5114D. Grooves, holes, or slots for supporting the optical fibers5114A-5114D may be formed in a support material (e.g., aluminum) by amachining process, such as electrical discharge machining (EDM). Thefiber support structure 5116 can be configured to bring the opticalfibers 5114A-5114D closer together so that when the light is output fromthe optical fibers 5114A-5114D the light is emitted from nearbylocations (e.g., about 110 to 140 microns apart, and more specifically,about 125 microns apart, although other distances are possible).

FIG. 13 is a cross-sectional view (shown from the position indicated byline 2-2 in FIG. 12) of an embodiment of optical fibers 5214A-5214D. Asshown in FIG. 13, the optical fibers 5214A-5214D can be single modeoptical fibers that have output ends measuring about 125 microns intotal diameter, with the core measuring about 3-4 microns in diameter.Other sizes can be used. In the embodiment shown in FIG. 13, the outputends of the optical fibers 5214A-5214D are brought close together sothat the cladding of one optical fiber is adjacent to the cladding ofthe next optical fiber, and light is emitted by the cores of opticalfibers 5214A-5214D at locations which have centers positioned about 125microns apart. Other arrangements are possible. It should be noted thatthe drawings herein are not drawn to scale (unless otherwise indicated),and in some embodiments the tapering of the optical fibers provided bythe fiber support structure 5116 can be much more pronounced than isindicated in FIG. 12.

In some embodiments, the fiber support structure 5116 does not bring theoptical fibers 5114A-5114D significantly closer together, but merelyorients the optical fibers 5114A-5114D so that light is emitted in adirection that causes the light to contact the optical elements5118A-5118D at a suitable angle. Other variations are possible.

Although the embodiment illustrated by FIG. 12 includes optical fibers5114A-5114D, other types of waveguides can be used (e.g., planarwaveguides). In some embodiments, the waveguides can be rigidwaveguides. The waveguides can include curved and/or linear paths. Thewaveguides can include a taper to otherwise have an output end withoutputs closer together than inputs at an input end, similar to theembodiment shown in FIG. 12. In some embodiments, an integratedwaveguide chip is used.

Although the embodiment illustrated in FIG. 12 shows the optical fibers5110A-5110D and the optical fibers 5114A-5114D as being different setsof optical fibers, in some embodiments, the optical system can include asingle set of optical fibers that extend through the housing and coupleto the laser light sources. In these embodiments, the optical inputports 5108A-5108D can be apertures in the housing 5102 through which theoptical fibers can pass. In some embodiments, the apertures can includeseals formed around the optical fibers to hermetically seal the interiorchamber. Epoxy may be used to provide such a hermetic seal, althoughother approaches can be used. The optical fibers can include opticalconnectors (e.g., FC/APC connectors) configured to removably couple withthe laser light sources 5112A-5112D.

The optical fibers 5114A-5114D (or waveguides) emit light toward aplurality of optical elements 5118A-5118D, which convert the light intobeams of light 5120A-5120D having a suitable shape and/or size. Theoptical elements 5118A-5118D can be lenses, and can be separateindividual lenses, or they can be conjoined forming a lens array. Insome embodiments, optical elements 5118A-5118D can be compactmicrolenses. In some embodiments, a single lens can be used to produceeach of the light beams 5120A-5120D. In some applications, it can beadvantageous to produce elongated beams of light, such as beams of lighthaving a generally elliptical cross-sectional shape (shown schematicallyin FIG. 12). For example, the beams of light 5120A-5120D can have agenerally Gaussian profile, so that when illuminating a flow cell, theintensity of the light illuminating the center of the flow cell issignificantly greater than the intensity of the light illuminating theperipheral edges of the flow cell. Accordingly, the beams of light5120A-5120D can be elongated (e.g., elliptical) beams, so that therelatively high intensity center regions of the light beams extendacross the entire width of the flow cell, while the relatively lowintensity outer regions of the light beams do not strike the flow cell.By using an elongated (e.g., elliptical) beam of light, a more uniformlateral distribution of light across the narrow width of the flow cellcan be achieved while illuminating a relatively small longitudinal areaalong the length of the flow cell and maintaining high light intensity.In some embodiments, the elliptical light beams can have a substantiallyelliptical cross sectional shape that measure about 5 to 15 microns inone direction and 55 to 100 microns in the other direction, or morespecifically about 10 microns in one direction and about 70 microns inthe other direction. Light beams of other shapes and sizes can be used.To produce elongated (e.g., elliptical) beams of light 5120A-5120D,optical elements 5118A-5118D can be anamorphic lenses (e.g., cylindricallenses) or Powell lenses (Gaussian to flat-top transformers). In oneembodiment, optical elements 5118A-5118D can be an anamorphic microlensarray. In some embodiments, the optical elements 5118A-5118D can beachromatic lenses. In some embodiments, optical elements 5118A-5118D canbe refractive and/or diffractive optical elements used to produce theelongated beams of light 5120A-5120D. In some embodiments, the opticalelements 5118A-5119D can be located adjacent to the output ends of theoptical fibers 5114A-5114D.

The optical system 5100 can include an output window 5121 that allowsthe beams of light 5120A-5120D to exit the internal chamber 5104. Insome embodiments, the housing 5102 includes an aperture 5122 in a wallthereof and the output window 5121 comprises a transparent window pane5124, positioned over the aperture 5122. The window pane 5124 can bemade from glass or acrylic or a variety of other transparent materials(e.g., plastic). The aperture 5122 and window pane 5124 can assume avariety of shapes, but in some embodiments they are circular orelliptical. The window 5121 can be attached to the housing 5102 by aplurality of fasteners such as bolts 5126. In FIG. 12, only two bolts5126 are shown in the cross-sectional view, but in some embodiments,additional bolts can be positioned along the edges of the window 5121.In some embodiments, the window 5121 can include a flange 5123 formounting the window. The flange 5123 may have a plurality of throughholes through which fasteners (e.g., bolts 5126) can pass to secure thewindow 5121 to the housing 5102. A seal 5128 (e.g., an O-ring) can bepositioned between the housing 5102 and the window 5121 (e.g., theflange 5123). The bolts 5126 can be tightened, causing the O-ring 5128to be compressed between the housing 5102 and the window 5121. In someembodiments, the O-ring 5128 produces a hermetic seal. Other approachescan be used to fasten the window 5121 to the housing 5102. For example,the window 5121 can be disposed in recess on the outer or inner surfaceof the housing 5102, or can be embedded into the housing 5102, or can bemounted onto the inside of the housing 5102. The window 5121 can besecured to the housing 5102 by an adhesive, epoxy, or cement.

Although the embodiment shown in FIG. 12 shows a single output window,multiple output windows can be used. For example, each beam of light5120A-5120D can exit the interior chamber 5304 via a respective outputwindow. In some embodiments, it is desirable that as much as possible ofat least the inner surface area of the housing 5102 comprise thethermally conductive material, to better achieve temperature uniformity.Accordingly, the output windows can be separated by thermally conductivematerial and can cover only as much area as necessary to allow lightbeams 5120A-5120D to leave the interior chamber 5104. However, in someembodiments a single output window is easier and less expensive toconstruct.

In some embodiments, the optical elements (e.g., lenses or lens) thatproduce the light beams 5120A-5120D can be formed as part of the outputwindow (or windows). For example, the window pane 5124 can include atleast one curved surface to produce optical power, which can beconfigured to produce the plurality of light beams 5120A-5120D having adesired shape and/or size. The window pane 5124 can comprise a lensarray such as a microlens array, and can be anamorphic as discussedabove.

The optical system 5100 can include a flow cell connector 5130 that isattached to the housing, and the flow cell connector 5130 is configuredto secure a flow cell 5132 so that it intersects the beams of light5120A-5120D. In some embodiments, the flow cell connector 5130 canpermanently attach the flow cell 5132 to the housing 5102. However, insome embodiments, the flow cell connector 5130 can allow the flow cell5132 to be removably attached to the housing 5102. In some embodiments,the flow cell connector 5130 can be compatible with multiple typesand/or sizes of flow cells. For example, the flow cell connector caninclude a clip, a friction or pressure fit coupling, a threaded portionconfigured to receive a corresponding threaded portion of the flow cell5132, or a variety of other connectors known in the art or yet to bedevised. The flow cell 5132 can be a capillary flow cell, and at leastpart of the flow cell can comprise a transparent material (e.g., glass)that allows the light beams 5120A-5120D to enter the flow cell 5132 andinteract with a sample fluid contained within the flow cell 5132. In oneembodiment, the flow cell 5132 can be a thin hollow tube, forming a flowpath that has a diameter of about 10 microns. Other flow cell typesand/or sizes can be used, and the flow cell 5132 can be orienteddifferently than as shown in FIG. 12. In some embodiments, the beams oflight 5120A-5120D strike the flow cell over areas centered about 110 to140 microns apart from each other, and in some embodiments, 125 micronsapart from each other. For some forms of optical measurements, it isdesirable for the laser light to strike the flow cell at specificlocations (e.g., areas spaced about 125 microns apart). In someembodiments, the optical system 5100 mounts the optical fibers toautomatically direct the light from the laser light sources 5112A-5112Dto the desired locations of the flow cell 5132 without requiring theuser to manipulate any mirrors or wavelength selective elements such asdichroic mirrors or optical elements.

The optical system 5100 can be compatible with various types of optical(e.g., spectroscopic) analysis. For example, for laser-inducedfluorescence spectroscopy, a fluorescent dye designed to bond with ananalyte can be introduced into the fluid sample. When the fluid samplepasses through the beams of light 5120A-5120D, the fluorescent dyeabsorbs photons and emits photons that have a longer wavelength (lessenergy). By using photodetectors such as a photomultiplier tube (PMT)(not shown) to measure the amount of light that is emitted, the presenceor concentration of the analyte in the sample fluid can be measured. Forabsorption spectroscopy, photodetectors (not shown) can be positioned onthe side of the flow cell 5132 opposite the housing 5102 to determiningthe amount of light that is absorbed by the fluid sample. The opticalsystem 5100 can also be compatible with other types of opticalmeasurements or spectroscopic analysis.

FIG. 14 schematically shows an embodiment of an optical system 5300 thatcan be used to direct light for optical measurements (e.g.,laser-induced fluorescence and spectroscopic analysis). The opticalsystem 5300 is similar to optical system 5100 in some aspects, andsimilar elements are labeled with the same reference numerals used inFIG. 12 except that the numbers are increased by 200. The optical system5300 can include a flow cell connector 5330 that comprises a thermallyconductive auxiliary sample housing 5350 which encloses an interiorchamber 5352. The flow cell connector 5330 can be configured to secure aflow cell 5332 so that it passes through the interior chamber 5352. Forexample, the sample housing 5350 can include two apertures 5354, 5356and two flexible seals 5358, 5360, so that the flow cell 5332 can beslidably inserted through the apertures 5354, 5356 and held in place byfriction against the flexible seals 5358, 5360. Alternatively, thesample housing 5350 can include a door allowing the sample housing 5350to be opened and the flow cell 5332 to be placed inside. In variousembodiments where the interior chamber 5352 of sample housing 5350 ishermetically sealed with respect to interior chamber 5304 of the mainhousing 5302, the interior chamber 5352 of the sample housing 5350 canbe exposed to ambient air without exposing the components containedwithin interior chamber 5304 of the main housing 5302. Accordingly, theinterior chamber 5352 of the sample housing 5350 can be exposed toambient air when flow cell 5332 is removed and the seals 5358, 5360 maybe excluded in some embodiments.

In some embodiments, the sample housing 5350 can be integrally formed aspart of the main housing 5302 or can be thermally coupled to the mainhousing 5302 so that the thermoelectric controller 5306 regulates thetemperature within the interior chamber 5352 of the sample housing 5350as well as the interior chamber 5304 of the main housing 5302. In someapplications it may be desirable to maintain the internal chamber 5352of the sample housing 5352 enclosing the flow cell at a differenttemperature than the internal chamber 5304 of the main housing 5302,such as when a fluid sample is used that should be maintained at adifferent temperature than the interior chamber 5304 of the main housing5302. Accordingly, in some embodiments, a second thermoelectriccontroller (not shown) can be thermally coupled to the sample housing5350 and an insulating layer (not shown) can be positioned at thetransition between the main housing 5302 and the sample housing 5350 sothat the internal chamber 5352 of the sample housing 5350 can bemaintained at a different temperature than the interior chamber 5304 ofthe main housing 5302.

The optical system 5300 can include a second output window fortransmitting light out of the internal chamber 5352 of the samplehousing 5350. The second output window can be similar to the outputwindow described above, and cover an aperture 5362 covered with atransparent window pane 5364. The transparent window pane 5364 can beattached to the housing 5350 by bolts 5366 and sealed by a seal 5368. Insome embodiments, the interior chamber 5352 of the sample housing 5350is not hermetically sealed and the seal 5368 can therefore be anon-hermetic seal or can be omitted altogether.

FIG. 15 schematically shows an embodiment of an optical system 5400 thatcan be used to direct light for optical measurements such aslaser-induce fluorescence and spectroscopic analysis. The optical system5400 is similar to optical systems 5100 and 5300 in some aspects, andsimilar elements are labeled with the same reference numerals used inFIGS. 12 and 14 except that the numbers are increased by 200 and 100respectively. Optical system 5400 can include a flow cell connector 5430that attaches a flow cell 5432 to the housing 5402 so that the flow cell5432 passes through the housing 5402. For example, the housing 5402 cancomprise two apertures 5454, 5456 and two flexible seals 5458, 5460, sothat the flow cell 5432 can be slidably inserted through the apertures5454, 5456 and held in place by friction against the flexible seals5458, 5460. Alternatively, the housing 5402 can include a door allowingthe housing 5402 to be opened and the flow cell 5432 to be placedinside. In some embodiments, the interior chamber 5404 can be exposed toambient air when flow cell 5432 is removed and the seals 5458, 5460 canbe non-hermetic seals. Also, the seal 468 can be a non-hermetic seal orcan be omitted altogether.

Part III

As noted above, U.S. Provisional Patent Application No. 62/133,241,filed Mar. 13, 2015, and U.S. Provisional Patent Application No.62/135,137, filed Mar. 18, 2015, are incorporated herein by reference intheir entireties, and the systems and methods described herein are alsodescribed therein. As described above, for example, with respect to FIG.7, beam adjusters 504A-504N such as Risley prism pairs 705A-705N may beemployed to adjust laser boresight and/or compensate for opto-mechanicalangular errors. However, in various implementations, other componentsmay be employed to adjust the laser boresight. For example, the beamadjusters 504A-504N of FIG. 5 can comprise a meniscus shaped opticalelement (e.g., a meniscus lens or meniscus window) to adjust boresightand/or to correct centration errors of one or more of the n laser beams.The meniscus shaped optical element can be tilted or translated (e.g.,in x and/or y directions) with respect to the optical path to alter theangle of the laser beam. The meniscus shaped optical element isdiscussed in detail below with reference to FIG. 16(a).

FIG. 16(a) illustrates an implementation of a multi-laser optical systemincluding a plurality of laser devices 101A, 101B, . . . , 101Nconfigured to emit light along a plurality of optical paths 102A, 102B,. . . , 102N respectively. A meniscus shaped optical element 1605A, isdisposed in at least one of the optical paths 102A. It is conceived thatall the optical paths 102A, 102B, . . . , 102N can include the meniscusshaped optical element. It is also conceived that one or more opticalpaths (e.g., optical paths 102B and 102N) can include Risley prism pairssimilar to Risley prism pairs 705A-705N as shown in FIG. 7 or Risleyprism pairs in combination with etalon plates similar to etalon plates707A-707N and/or 708A-708N as shown in FIGS. 8A and 8B instead of themeniscus shaped optical element. It is also conceived that the meniscusshaped optical element can be disposed along with the Risley prism pairsand/or the etalon plates. For example, a meniscus shaped optical elementand one or more etalon plates (e.g., orthogonally oriented tilted etalonplates for translating the beam in orthogonal x and y directions) can bedisposed in the same optical path such that a beam from one of the laserdevices passes through each of the meniscus shaped optical element andthe one or more etalon plates.

FIG. 16(b) illustrates an implementation of a meniscus shaped opticalelement 1605A including a first curved surface 1607 configured toreceive the incident laser beam and a second curved surface 1609opposite the first curved surface 1607 configured to output the laserbeam. The first curved surface 1607 and the second curved surface 1609can be portions of a spherical surface. Alternately, the first curvedsurface 1607 and the second curved surfaces can be aspheric. The firstand second curved surfaces can also be cylindrical surfaces and havedifferent curvature in different directions (e.g., in x and ydirections). In some embodiments, the first and second curved surfacescan have non-zero curvature in different directions (e.g., in x and ydirections); for example, the first and second curved surfaces can beellipsoidal curved surfaces or toroidal curved surfaces. The first andthe second surface 1607 an 1609 can be associated with a radius ofcurvature or an aspheric equation. In various implementations, the firstand the second surfaces can have almost identical surfacecharacteristics. For example, the curvature, the surface sag, and/or theradius of curvature of the first and the second surface 1607 and 1609can be identical. In various implementations, the radius of curvature ofthe first curved surface 1607 and the radius of curvature of the secondcurved surface 1609 can be approximately equal. In variousimplementations, the first and the second surface of the optical element1605A can be shaped and sized identically at least sufficiently closesuch that the optical element 1605A has zero optical power.Additionally, the thickness of the optical element 1605A can also beshaped and sized identically at least sufficiently close such that theoptical element 1605A has zero optical power. In other implementations,the surface characteristics of the first and the second surface of theoptical element 1605A can deviate slightly from each other such that theoptical element 1605A has almost no optical power. For example, themeniscus optical element may have a optical power larger than zero butless than 2 diopter, less than 1 diopter, or less than 0.1 diopter, orany ranges therebetween. As illustrated, the first surface 1607 isconvex and the second surface 1609 is concave. However, it is conceivedthat the first surface 1607 is concave and the second surface 1609 isconvex. For example, the first curved surface 1607 and the second curvedsurface 1609 may have a radii of curvature larger or equal to 10 mm andless than or equal to 1000 mm. Values outside these ranges are alsopossible. Additionally, as another example, the optical element 1605Amay have thickness greater than or equal to 2 mm and less than or equalto 20 mm. Values outside these ranges are also possible.

The first surface 1607 and the second surface 1609 is intersected by anoptical axis 1611. The optical axis 1611 can pass through the center ofcurvature of the first surface 1607 and the center of curvature of thesecond surface 1609. Without any loss of generality, the optical axis1611 can represent a principal axis of the optical element 1605A. Anyray of light that is incident along the optical axis 1611 will passthrough the optical element without being deviated. The optical axis1611 can intersect the first surface 1607 at a first vertex and thesecond surface 1609 at a second vertex. The optical element 1605A can beconfigured such that a length of a segment joining the first vertex andthe second vertex is less than, greater than, or equal to the length ofany other parallel segment, depending for example, on whether themeniscus lens is a positive meniscus lens (center thickness larger thanedge thickness) or negative meniscus lens (with center thickness smallerthen edge thickness). In various implementations, the thickness of theoptical element 1605A can be measured along the optical axis and beequal to the length of the segment joining the first vertex and thesecond vertex. Various implementations of the optical element 1605A canbe configured to be rotationally symmetric about the optical axis 1611.

In various embodiments, the optical element 1605A can be used toredirect optical beams. In various embodiments, an incoming light beam(e.g., an output of the laser 101A) is incident on the optical element,experiences refraction and redirection under Snell's Law, and exits theoptical element. It should be noted that the incoming light beam may notexperience any refraction and redirection if it is normally incidentalong the optical axis. In some configurations, the output beam mayexperience an elevation deviation without with respect to the inputbeam. In certain configurations of the optical element, it may also bepossible to control the angle of deviation in the lateral (e.g., left orright) direction of the output beam. Therefore, the optical element1605A can be used to direct a light beam at a variety of elevationangles and lateral angles (left or right versus up or down directions).Viewed from another perspective of another coordinate system, theoptical element 1605A can be used to direct a light beam at a particularazimuth angle and a particular elevation. This is explained in furtherdetail below.

The optical element 1605A can be configured to correct boresight errorsof the laser beam output from the laser 101A along optical path 102A.The adjusted laser beam can be positioned and/or combined into a desiredspatial arrangement with other laser beams output along optical paths102B, . . . , 102N by the beam positioning/combining system 1000. Invarious embodiments, the errors in the laser boresight andopto-mechanical angular errors may be compensated for by tipping ortilting the optical element 1605A (adjusting the pitch and/or yaw of theoptical element 1605A) with respect to the incident laser beam or theoptical path and/or by adjusting the position of the optical element1605A horizontally and/or vertically with respect to the incident laserbeam or the optical path. For example, as discussed in detail below, invarious implementations, the optical element 1605A can be tipped and/ortilted with respect to the optical path to compensate for errors in theboresight of the laser beam output. As another example, as discussed indetail below, in various implementations, the position of the opticalelement 1605A can be adjusted laterally vertically and/or horizontallywith respect to the incident laser beam or the optical path to correctfor boresight error in the incident laser beam. The thickness of theoptical element 1605A along the optical axis and/or characteristics ofthe first and the second curved surface 1607 and 1609 (e.g., curvature,radius of curvature, apshericity) can be selected to provide a desiredrange of correction. In various elements, the thickness of the opticalelement 1605A along the optical axis and/or characteristics of the firstand the second curved surface 1607 and 1609 (e.g., curvature, radius ofcurvature, apshericity) can be selected to provide a desired correctionrange, correction sensitivity and/or correction resolution.

FIG. 16(c-1) depicts a laser beam with 0 degree boresight error that isincident on an implementation of an optical element 1605A. The opticalelement 1605A is configured such that the incident beam of light passesthrough the optical element 1605A without being deviated such that theoutput laser beam also has 0 degree boresight error. In the illustratedimplementation, the laser beam is incident along a direction parallel tothe z-axis. The optical element 1605A is positioned such that theoptical axis 1611 is along the z-axis and the first and the secondsurface of the optical element 1605A extend vertically and horizontallyin the x and y directions.

FIG. 16(c-2) depicts a laser beam with about 1 degree boresight errorthat is incident on an implementation of an optical element 1605A. Inother words, the incident laser beam can be at an angle of about 1degree with respect to the z-axis. The optical element 1605A can berotated with respect to the incident beam (e.g., about the x-axis, aboutthe y-axis or about the x-axis and the y-axis) such that the incidentlaser beam is output from the optical element 1605A after refraction atthe first surface 1607 and the second surface 1609 with a boresighterror less than 1 degree (e.g., boresight error less than 0.5 degrees ora 0 degree boresight error). In the illustrated implementation, theoptical element 1605A is rotated about the y-axis (or tipped) withrespect to the x-axis by an angle of about 29.6 degrees to achieve 0degree boresight error, as shown in FIG. 16(c-3). In variousimplementations, the thickness along the optical axis of the opticalelement 1605A, the surface characteristics (e.g., curvature, radius ofcurvature, surface sag, etc.) can be configured such that the opticalelement is tipped by a different amount to achieve the same amount ofcorrection. For example, in various implementations, the optical element1605A can be tipped by an angle between about 0 degrees and 30 degreesto correct the boresight error from about 0 degrees to a boresight errorless than 0.05 degree or between about 0 degrees and 30 degrees tocorrect the boresight error from about 0 degrees to a boresight errorless than 5 degrees. The sensitivity can thus range between about 0.0017degrees/degree and 0.17 degrees/degree. The range of correction canrange between 0 degrees and 0.05 degrees or between about 0 degrees and5 degrees. Values outside these ranges are also possible.

FIG. 16(d-1) illustrates the variation in the boresight angle changeexpressed in radians (rad) versus the change in the angle of incidence(AoI). The AoI corresponds to the relative angle of incidence of thelaser beam with respect to the meniscus optical element expressed indegrees for an implementation of a cylindrical meniscus shaped opticalelement. The cylindrical meniscus optical element in this example may becurved in one direction, for example, in the x-z plane. The variation inthe boresight angle change with respect to the change in the angle ofincidence (AoI) is obtained using a simulation program such as Zemax. Asnoted from FIG. 16(d-1), the boresight angle correction is about 2.7E-3when the relative angle of incidence of the laser beam with respect tothe meniscus optical element is about −30 degrees and the boresightangle correction is about −2.7E-3 when the relative angle of incidenceof the laser beam with respect to the meniscus optical element is about30 degrees. From FIG. 16(d-1) it is understood that by changing therelative angle of incidence of the laser beam with respect to themeniscus optical element between about −30 degrees and 30 degrees, theboresight angle can be changed in a range between about −2.7E-3 andabout 2.7E-3 in this example.

FIG. 16(d-2) illustrates the variation in the boresight angle changeexpressed in milliradians (mrad) versus the change in the angle ofincidence (AoI) which corresponds to the relative angle of incidence ofthe laser beam with respect to the meniscus optical element expressed indegrees measured for an implementation of a cylindrical meniscus shapedoptical element. The cylindrical meniscus optical element in thisexample may be curved in the x-z plane. The measured variation in theboresight angle change with respect to the change in the angle ofincidence (AoI) is compared with the simulated variation represented bycurve 1615 similar to the curve shown in FIG. 16(d-1). As noted fromFIG. 16(d-2), because the meniscus optical element is a cylindricaloptical element curvature only in one direction, e.g., along the x-zplane, a change in the angle of incidence (AoI) along in the x-z plane(tip) brings about a greater change in the boresight angle as depictedby curve 1621 as compared to a change in the boresight angle broughtabout by a change in the angle of incidence (AoI) in the y-z plane(tilt) depicted by curve 1618. Furthermore, it is observed that thesimulated change in boresight angle with respect to a change in theangle of incidence (AoI) depicted by curve 1615 corresponds with themeasured change in the boresight angle brought about by a change in theangle of incidence (AoI) along the x-axis depicted by curve 1621.

FIG. 16(d-3) illustrates the measured variation in the boresight angleof an output laser beam expressed in milliradians (mrad) as a functionof tilt about the x-axis of an implementation of a spherical meniscusshaped optical element depicted by curve 1625. The surfaces of theimplementation of the spherical meniscus shaped optical element eachhave a radius of curvature of about 51.9 mm. The implementation of thespherical meniscus shaped optical element has a thickness of about 5 mm.In FIG. 16(d-3), the variation in the boresight angle of an output laserbeam as a function of tilt about the x-axis for a simulatedimplementation of a spherical optical element having surfaces with aradius of curvature of about 51.9 mm and thickness 5 mm is depicted bycurve 1630. It is noted from FIG. 16(d-3) that the measured variation inthe boresight angle of an output laser beam as a function of tilt aboutthe x-axis for the implementation of a spherical meniscus shaped opticalelement agrees with the simulated variation. It is further noted that atilt about the x-axis between about −3 degrees and +3 degrees canproduce a change in the output beam angle between about −1.75 mrad and+1.75 mrad.

FIG. 16(d-4) illustrates the measured variation in the boresight angleof an output laser beam expressed in milliradians (mrad) as a functionof being tipped about the y-axis of an implementation of a sphericalmeniscus shaped optical element depicted by curve 1635. The surfaces ofthe implementation of the spherical meniscus shaped optical element eachhave a radius of curvature of about 51.9 mm. The implementation of thespherical meniscus shaped optical element has a thickness of about 5 mm.In FIG. 16(d-4), the variation in the boresight angle of an output laserbeam as a function of rotation about the y-axis for a simulatedimplementation of a spherical optical element having surfaces with aradius of curvature of about 51.9 mm and thickness 5 mm is depicted bycurve 1640. It is noted from FIG. 16(d-4) that the measured variation inthe boresight angle of an output laser beam as a function of rotationabout the y-axis for the implementation of a spherical meniscus shapedoptical element agrees with the simulated variation. It is further notedthat a tip about the y-axis between about −3 degrees and 3 degrees canproduce a change in the output beam angle between about +1.75 mrad and−1.75 mrad.

FIG. 16(e-1) depicts a laser beam with about 0.5 degree boresight errorthat is incident on an implementation of an optical element 1605A. Theoptical element 1605A can be translated vertically with respect to theincident beam (e.g., translated parallel to y-axis) such that theincident laser beam is output from the optical element 1605A afterrefraction at the first surface 1607 and the second surface 1609 with aboresight error of substantially 0 degrees. FIG. 16(e-2) illustrates animplementation of a translated configuration of the optical element1605A. In the translated configuration, the optical element 1605A isdisplaced vertically upwards (e.g. upwards along the y-axis) withrespect to the incident laser beam by about 2.9 mm. In variousimplementations, the thickness along the optical axis of the opticalelement 1605A, the surface characteristics (e.g., curvature, radius ofcurvature, surface sag, etc.) can be configured such that the opticalelement is displace by a different amount to achieve the same amount ofcorrection. For example, in various implementations, the optical element1605A can be displaced vertically upwards (along the +x-axis) ordownwards (along the −x-axis) by a distance between about 0 mm and 10 mmto correct the boresight error from about 0 degrees to a boresight errorless than 1.5 degrees. In various implementations, the optical element1605A can be displaced vertically and/or horizontally (e.g., along the±y-axis and/or ±x-axis) by a distance between about 0 mm and 10 mm tocorrect the boresight error from about 0 degrees to a boresight errorless than 0.01 degrees. The sensitivity can thus range between about0.15 degrees/mm and 0.001 degrees/mm. The range of correction can rangebetween 0 degrees and 1.5 degrees or between about 0 degrees and 0.01degrees. Values outside these ranges are also possible.

In the multi-laser system 100 shown in FIG. 16(a), a plurality ofoptical paths are depicted. A first optical path originates at laser101A, passes through the optical element 1605A, where laser boresightand opto-mechanical angular errors may be compensated through adjustmentof the angle of incidence of the laser beam relative to the opticalelement 1605A and then arrives at the beam combining/positioning system1000. The adjustment of the angle of incidence of the laser beamrelative to the optical element 1605A can be accomplished by rotatingthe optical element 1605A (e.g., by adjusting the pitch and/or yaw ofthe optical element 1605A), and/or by translating the optical element1605A with respect to the incident optical beam. A second optical pathoriginates at laser 101B, passes through the Risley prism pair 705A,where laser boresight and opto-mechanical angular errors may becompensated through adjustment of the wedge angles of and the azmiuthalrotation between the prism pair 705A, and then arrives at the beamcombining/positioning system 1000. An N-th optical path originates atlaser 101N, passes through the Risley prism pair 705N, where laserboresight, and opto-mechanical angular errors may be compensated throughadjustment of the wedge angles of the prism pair 705N, passes throughglass etalon plates 707N, 708N, where laser centration andopto-mechanical lateral positioning errors may be compensated for byadjusting the pitch and/or yaw of the glass etalon plates 707N and/or708N, and then arrives at the beam combining/positioning system 1000. Asdiscussed above, meniscus optical elements may replace the Risleyprisms. Accordingly, glass etalon plates 707N and/or 708N may be used incombination with meniscus optical elements to alter the vertical and/orhorizontal beam position and/or correct centration error.

Propagating along these paths, laser beams 102A-102N, which may haveoriginally been far from one another, are repositioned to be closertogether as beams 1001A-1001N. In some embodiments, the beams1001A-1001N are parallel to one another. In other embodiments, the beams1001A-1001N are not parallel to one another. Other optical components(e.g., lenses, prisms, polarization rotators, waveplates, etc.) can beincluded to alter the laser beams and/or optical paths.

The optical element 1605A can comprise materials that are transparent tothe wavelength of the incident light (e.g., wavelength of the outputfrom the lasers 101A, 101B, . . . , 101B). For example, the opticalelement 1605A can include materials such as glass, polymer,polycarbonate, polyethylene terephthalate, glycol-modified polyethyleneterephthalate, amorphous thermoplastic, and/or other substrates.

Implementations of optical element 1605A may be useful for systems suchas described above or in spectroscopic analysis systems such as thesystems disclosed in U.S. Publication No. 2014/0160786 which isincorporated herein by reference in its entirety. The implementations ofoptical element 1605A can also be used in other systems and devices aswell and thus may be used independently of the systems described above.Other variations are also possible.

In various implementations, the plurality of lasers 101A, 101B, . . . ,101N; the beam positioning system 1000, the optical element 1605A, theRisley prism pair 705A, the etalon plate 707N, 708N can be enclosed in athermally stable enclosure 150. In various implementations, thethermally stable enclosure 150 can include a material having a thermalconductivity of at least 5 W/(m K). The thermally stable enclosure 150can be configured to maintain alignment of the laser beams to a targetobject 1100 over a range of ambient temperatures. In some embodiments,the optical fibers can be employed to direct light to the flow cell.Other variations are also possible. Similarly, in any method or processdisclosed herein, steps or operations can be add, removed, and/orrearranged.

Part IV

As noted above, U.S. Provisional Patent Application No. 62/133,241,filed Mar. 13, 2015, and U.S. Provisional Patent Application No.62/135,137, filed Mar. 18, 2015, are incorporated herein by reference intheir entireties, and the systems and methods described herein are alsodescribed therein. As described above, for example, with respect to FIG.2, the multi-laser system 100 may include optional beam focusing optics117 to provide size reduction and/or shaping to the output laser beams118, 119, 120. For example, the focusing optics 117 may change the shapeof the laser beams. In some embodiments, for example, the laser beams118, 119, 120 can have a generally Gaussian profile, so that whenilluminating a flow cell, the intensity of the light illuminating thecenter of the flow cell is significantly greater than the intensity ofthe light illuminating the peripheral edges of the flow cell.Accordingly, in various configurations, an optical component may beemployed to convert the Gaussian beam into a beam having a flat topprofile. Additionally, having the beams of light 118, 119, 120 withelongated cross-sections that produce an elongated, for example, linearor line shaped spot size, so that the light extends further across thewidth of, for example, a flow cell may be desirable. By using a beamwith an elongate cross section and spot shape, for example, having theshape of a line, and having a flat top distribution, a more uniformdistribution of light across the width of the flow cell or other targetoutput can be achieved while illuminating a relatively smalllongitudinal area along the length of the flow cell and maintainingsubstantially uniform high light intensity. See also FIG. 12 and thediscussion of the optical elements 5118A-5118D.

In various configurations, a Powell lens may be used to convert aGaussian beam into a beam having an elongated (e.g., line-shaped)cross-section and spot with a flat top distribution. A change in thesize of the beam incident on the Powell lens, for example, a change inthe beam width as a result of aging of the laser may, however, alter theoutput of the Powell lens. A description of a component that includes aPowell lens and that is configured to be adjustable to accommodate forchanges in beam size of the input laser beam is provided below. Anexample Powell lens is disclosed in U.S. Pat. No. 4,826,299.

Such a component may be useful for systems such as described above, forexample, in either or both Part I and Part II, but may be used in othersystems and devices as well and thus may be used independently of thesystems described above. Variations are also possible.

FIGS. 17A and 17B depict example embodiments of laser systems in which aPowell lens is used. In the embodiment of FIG. 17A, a laser 1705 emits alaser beam 1707, which is incident on a beam focusing opticsconfiguration: a negative lens 1709, a Powell lens 1710, and a positivelens 1711. In some configurations, the negative lens 1709 and thepositive lens 1711 can be an afocal system such as a telescope opticaldesign and may be a Galilean configuration. In various embodiments,other lenses can be used as part of this beam focusing optics. In somesituations, this incident laser beam 1707 on the negative lens 1709 canbe referred to as an input to the beam focusing optics configuration.Similarly, in some situations, output laser beam 1712 can be viewed asan output of the beam focusing optics unit. In another embodiment, thenegative lens 1709 and positive lens 1711 can be rearranged in position,for example locations of the positive lens and negative lens may bereversed with the positive lens receiving the laser beam prior to thenegative lens. In some configurations the negative lens 1709 and thepositive lens 1711 are separated by the difference in the absolute valueof their respective focal lengths. Accordingly, if you treat thenegative lens 1709 as having a negative focal length, the distancebetween the negative lens and the positive lens 1711 is the sum of thefocal lengths. Variations of in the design of the beam focusing opticsare possible.

In various embodiments, the output laser beam 1712 can have a Gaussianbeam profile. The Powell lens 1710 is configured to convert theresulting laser beam of negative lens 1711 that has a Gaussian beamprofile into a laser beam having a flat top intensity distribution andan elongated cross-section orthogonal to propagation of the beam, withthe elongated cross-section having a length in a first direction that islonger than in a second orthogonal direction. The Powell lens 1710,however, is sensitive to the size of the Gaussian beam and performanceis improved for that particular size beam. However, with time a laserages and the beam size changes. The negative lens 1709 is thereforeconfigured to alter the beam size of the laser beam 1707 in at least onedirection. The Powell lens 1710 can then convert the laser beam exitingthe negative lens 1711 and incident on the Powell lens that has aGaussian beam profile into a laser beam having a flat top intensitydistribution and an elongated cross-section orthogonal to propagation ofthe beam. This elongated cross-section has a length in a first directionthat is longer than in a second orthogonal direction. The output laserbeam 1712 from the Powell lens 1710 subsequently propagates to thepositive lens 1711. The positive lens 1711 is configured to collimatethe laser beam from the Powell lens 1710 in at least in one direction.In various embodiments, the negative lens 1711 and positive lens 1709can be cylindrical lenses.

To accommodate variation in the beam size output by the laser beam, forexample, over time, the Powell lens 1710 is coupled to a translationstage 1715. This translation stage 1715 can move the Powell lens 1710 sothat the diameter of the laser beam 1707 incident on the Powell lens1710 can be adjusted to a size for which the Powell lens performs wellby producing the desired elongated (e.g., linear) spot having a flat topintensity distribution. In the configurations shown in FIG. 17A, thelaser beam 1712 after passing through the Powell lens 1710 and thepositive lens 1711 is received by a target 1725, and subsequently adetector 1720.

In some configurations, the detector 1720 can transmit a detector outputsignal 1727 to a control system 1735, which may include an imageprocessing unit 1730. The control system 1735 can process the signal1727 as feedback. With this feedback processed in image processing unit1730, the control system can determine whether an adjustment to thetranslation stage 1715 may be helpful. An adjustment to the position ofthe translation stage 1715, for example, along the longitudinal axis ofthe Powell lens, (e.g., along the z-axis) can be determined based on thefeedback. Such an adjustment can move the translation stage along thez-axis (e.g., in a longitudinal direction along the optical axis laserbeam 1707) to a z-axis plane where the output received by the detectoris has a more linear shaped spot and/or a more flat top distribution.

The control system 1735 can generate and send one or more controlsignals 1737 to the translation stage 1715 to adjust the translationstage in position (e.g., a movement of the position of the translationstage 1715), thereby adjusting the Powell lens in position. Because thefirst lens in the beam focusing system, the negative lens 1709 in FIG.17A causes the beam to diverge, the change in the position of the Powelllens 1710 and the distance of the Powell lens from the negative lens canresult in a change in diameter of the laser beam 1707 incident on thePowell lens.

Control system 1735 can use the image processing result generated byimage processing unit 1730 to generate one or more signals configuredfor use at the translation stage 1715. The one or more signals can becommunicated as an electrical signal (e.g., a series of varyingvoltages) as the signal to the translation stage 1715. In various otherembodiments, the one or more signals can be communicated (depicted asalternating dotted line in FIG. 17A) via a wireless medium, an opticalmedium (e.g., a fiber optic cable), etc. The one or more signals canadjust the position of the translation stage 1715 in a longitudinaldirection along the z-axis (or possible in lateral directions, e.g., ineither the x-axis or y-axis, as discussed herein). In some embodiments,the one or more signals can correspond to a two-dimensional movement ora three-dimensional movement of the translation stage 1714. Inparticular, in some configurations, a movement in the Powell lens 1710in a lateral direction, in response to one or more signals (e.g., acontrol signal), can adjust the angular direction of the laser beam 1707incident on the negative lens 1709. Such an adjustment can, in somecases, reduce boresight error and/or to adjust the centration of thelaser beam 1707.

The laser 1705 may comprise a diode laser, a solid-state laser, afrequency-doubled laser, and/or another types of laser. Laser 1705 canoutput a laser beam 1707. Laser beam 1707 can propagate to Powell lens1710, with the laser beam having a portion of the beam width incident ona roof of the Powell lens 1710.

Powell lens 1710 can include other types of Powell lens. The Powell lens1710 can convert laser beam 1705 that has a Gaussian beam profile intothe output laser beam 1712 having a flat top intensity distribution andan elongated cross-section orthogonal to propagation of the beam, withthe elongated cross-section having a length in a first direction that islonger than in a second orthogonal direction. Some examples of Powelllenses are discussed in U.S. Pat. No. 4,826,299. In some embodiments,the Powell lens includes a surface having an apex resembling a curvedroof line. Such a lens can generate a line shaped beam cross-section orspot. In some embodiments, the surface having the rounded roof shapedsurface (referred to herein as a roof having a roofline with a roofangle or apex angle) is a complex two-dimensional aspheric curve. Insome embodiments, this two-dimensional aspheric curve generatesspherical aberration that redistributes the light along a line. Thisspherical aberration may also cause a decrease in the light in thecenter of the line and an increase in the light at the ends of the line.In various configurations, the light fans out at a fan angle that is afunction of the refractive index of the lens material and the roofangle. For example, in some cases a steeper roof and higher refractiveindex of the lens material causes a wider fan angle increases the lengthof the line.

Target 1725 may comprise a flow cell, a flow cell mount, a light pipe, awaveguide, an optical fiber, or a lab on a chip. In some embodiments,the target object may comprise a mounting mechanism, mounting system(e.g., mounting alignment system), etc. for a flow cell, a flow cellmount, a light pipe, a waveguide, an optical fiber, and/or a lab on achip. Target 1725 can be a translucent medium that can further propagateoutput laser beam 1712 to detector 1720 (depicted as a dotted line inFIG. 17A).

Detector 1720 can be a photodetector array that detects the beam passingthrough a target 1725, for example, the target 1725 can be a flow cellwith a liquid medium that may transmit the beam 1712 outputted from thebeam focusing optics comprising the Powell lens 1710. The detector 1720can transmit a signal 1727. Signal 1727 can be transmitted in a varietyof ways. In some embodiments, detector 1720 is a photodetector thattransmit the signal 1727 as an electrical signal (e.g., a voltage).Detector 1720 can also include a wireless transmitter that transmitssignal 1727 as a wireless signal. Or in another embodiment, detector1720 can include an RF transmitter that transmits 1727 as an RF signal.As can be seen by this description, various methods of communicatingsignal 1727 from detector 1720 are possible in the laser system 1700(depicted as alternating dotted line in FIG. 17A).

Control system 1735 receives at least signal 1727 to be used as feedbackfor the laser system 1700. Control system 1730 can use the feedback todetermine whether to adjust the position of translation stage 1715. Invarious embodiments, image processing unit 1730 can uses various imageprocessing approaches to process signal 1727, and thereby generate animage processing result that is assessed by the control system whichproduces a control signal for driving the translator as a result. Insome configurations, control system 1735 can include a user interfacethat displays the optical power distribution. A signal for driving thetranslation stage based on input from the user having seen the opticalpower distribution (or shape of the laser spot) can be produced by thecontrol system. As discussed above, for example, in some cases, theoptical power distribution can be a uniform line (e.g., a uniform linehaving a flat top optical signal 1712 outputted by the Powell lens). Inother cases, the optical power distribution can be a non-uniform (e.g.,the power distribution is split into at least two peaks with a higherpower concentrated in these portions corresponding to a distortion inthe optical signal 1712 outputted from the Powell lens) or the spot maynot be a line.

In some embodiments, human intervention is not needed and feedback fromthe detector can be use by the control system to automatically adjustthe translation stage such that improved output is obtained at thetarget. In some configurations, for example, control system 1735 candetermine that the image processing result generated by image processingunit 1730 corresponds to a distortion in the optical beam 1712. Thisdistortion can result from a change of the diameter of laser beam 1707incident on the Powell lens 1710. With this distortion identified,control system 1735 can determine, possibly using an iterative ordithering process, a change in the position of the translation stage1750 that improves the optical beam by changing the position of thePowell lens 1710 and changing in the diameter of the laser beam 1707. Achange in the diameter of the laser beam 1707 can result, for example,in a more uniform power distribution of optical signal 1712 (e.g., asubstantially uniform power distribution). A uniform power distributioncan result in a more optimal testing condition for biological samplesbeing tested at flow cell 1725. Accordingly, the control system 1730 canuse the feedback to create a control system loop that maintains theposition of the translation stage so that a uniform power distributionor more desirable spot shape (e.g., linear) is maintained on the target1725. The detector 1720 can continue to receive the optical signal thatcan indicate, after processing by the control system 1730, whether ornot a loss of power has occurred at the flow cell, whether or not thepattern of the power distribution has changed at the flow cell, orvarious other measurements that can be used by the control system 1730to maintain an optimal optical properties (e.g., a power distribution)emanating from Powell lens 1730.

As discussed above, in various embodiments, the one or more signals canbe received via user input as part of a user interface associated withcontrol system 1735. For example, in one embodiment, control system 1735can include a display configured to display information based on theoptical image of the cross-sectional shape and/or intensity distributionof the output laser beam 1712 for a user to view. In one embodiment, thedisplay can show the image processing result (e.g., a representation ofthe optical image) generated by image processing unit 1730. The user canthen determine whether the translation stage is to be translated andinput information into the user interface to move the translation stage1715. In other embodiments, the one or more signals can be automaticallyand/or dynamically determined when control system 1735 receives feedbackfrom detector.

Translation stage 1715 can be any mechanical apparatus or device capableof moving an attached lens. For example, translation stage 1715 caninclude an actuator that receives and can respond to a control signal(e.g., one or more signals a control system 1735). The actuator can be amotor or piezo device that can generate a force that actuates movementof the translation stage 1715, thereby moving the Powell lens 1710coupled to the translation stage 1715. As discussed above, in someconfigurations, the translation stage 1715 can move to adjust theangular and/or lateral position of the laser beam 1707 so that theboresight and centration errors of the laser 1705 are compensated for.

FIG. 17B depicts an example embodiment of a multi-laser system. Themulti-laser system 1750 depicted in FIG. 17B comprises a thermallystable, temperature controlled enclosure 1757 configured to mechanicallyand/or thermally couple to a target object 1778. The enclosure 1757helps to isolate the laser and optics within the enclosure 1757 from theambient environment, which may have varying temperature. In someembodiments, the target object may comprise a flow cell, a flow cellmount, a light pipe, a waveguide, an optical fiber, or a lab on a chip.In some embodiments, the target object may comprise a mountingmechanism, mounting system (e.g., mounting alignment system), etc. for aflow cell, a flow cell mount, a light pipe, a waveguide, an opticalfiber, and/or a lab on a chip.

The multi-laser system 1750 includes a plurality of lasers 1751A-1751C,enclosed within the thermally stable enclosure 1757. The plurality oflasers 1751A-1751C may comprise diode lasers, solid-state lasers,frequency-doubled lasers, and/or other types of lasers. The plurality oflasers 1751A-1751C output a plurality of respective laser beams1752A-1752C. Each of the laser beams 1752A-1752C may have a wavelengthdifferent from the other laser beams.

In some embodiments in which the system 1750 is used perform testing ofbiological samples, flow cells are illuminated with the laser beam 1766.Fluorescent dyes absorb light at certain wavelengths and in turn emittheir fluorescence energy at a different wavelength. This emission canbe detected to ascertain properties of the fluid in the flow cell.

The system shown in FIG. 17B includes beam focusing optics comprising anegative lens 1760, a Powell lens 1762, and a positive lens 1764 canassist in acquisition of test results. As discussed above, the negativelens 1760 and a positive lens 1764 may be arranged to form an afocalsystem. For example, the negative lens 1760 and a positive lens 1764 maybe arranged to form a telescope such as Galilean configuration. In someconfigurations, for example, the negative lens 1760 and positive lens1764 are separated by the distance that is the difference of theabsolute value of their respective focal lengths. In otherconfigurations, the negative lens 1760 and positive lens 1764 can bereversed in position, with the positive lens prior to the Powell lensand the negative lens after the Power lens in the optical path from thelaser to the target. Variations in the telescope design or the beamfocusing optics are possible.

The multi-laser system 1750 also includes a beam combiner 1755 thatoutputs a laser beam 1758 with the wavelengths of the plurality of laserbeams 1752A-1752C. The laser beam 1758 propagates to the beam focusingoptics comprising the negative lens 1760, the Powell lens 1762 coupledto the translation stage 1765, and the positive lens 1764, with anoutput laser beam 1766. In various embodiments, the output laser beam1766 can have a Gaussian beam profile. The negative lens 1760 isconfigured to alter the beam size of the laser beam 1758 in at least onedirection. The Powell lens 1762 is configured to convert the resultinglaser beam of negative lens 1760 that has a Gaussian beam profile into alaser beam having a flat top intensity distribution and an elongatedcross-section orthogonal to propagation of the beam, with the elongatedcross-section having a length in a first direction that is longer thanin a second orthogonal direction. The positive lens 1764 is configuredto collimate the laser beam from the Powell lens 1762 in at least in onedirection. In various embodiments, the negative lens 1762 and positivelens 1764 can be cylindrical lenses.

The laser beam 1766 propagates to a beam splitter 1768 that receives thelaser beam and splits the laser beam into at least one beam that isdirected to the detector 1770 and at least one beam to the target 1778.The detector 1770 is disposed to receive an image of the cross-sectionalshape and intensity distribution of the laser beam 1766. As describedabove with respect to FIG. 17A, the detector 1770 can be a photodetectorarray that sends a signal 1772 (e.g., an optical image) to controlsystem 1780. Further, signal 1772 can be transmitted in a variety ofmethods/ways as described with respect to FIG. 17A and depicted as analternating dotted line.

Control system 1780 is configured to provide the control signal 1790 toadjust translation of the translation stage 1765 based on analysis bythe image processing unit 1782 of the image received by the detector1770. The control system 1780 can also be configured to receive inputfrom a user, and, in turn, provide the control signal 1790 to adjusttranslation (e.g., a position) of the translation stage 1765 based onthe input from a user. Further, control signal 1790 can be transmittedin a variety of methods/ways as described with respect to FIG. 17A anddepicted as an alternating dotted line.

The translation stage 1765 is configured to translate the Powell lens1762 in a longitudinal direction either closer to the negative lens 1760and farther from the positive lens 1764, or farther from the negativelens 1760 and closer to positive lens 1764 in the control signal 1790.Additionally, translation stage 1765 can be configured to translate thePowell lens 1762 in a lateral direction in response to the controlsignal 1790 to adjust angular direction of the laser beam 1758 to reduceboresight error and/or to adjust the centration of the laser beam 1758.As described above with respect to FIG. 17A, variations of thetranslation stage 1765 are possible.

FIG. 18 depicts an exemplary method 1800 using a Powell lens system aspart of a laser system. For example, system 1700 or system 1750 depictedin FIGS. 17A and 17B respectively can use the flow of the Powell lensadjustment routine to adjust the position of the Powell lens in theirrespective systems. This process may be performed automatically usingfeedback from a detector or manual by a user who evaluates the opticalbeam received by the detector and based on such evaluation provides acontrol signal to the translation stage. In the later case, the user maybe located remotely and the system need not be opened to adjust thePowell lens and the beam.

A wide variety of other variations are possible. Components can beadded, removed, and/or rearranged. For example, in some embodiments, theoptical system does not include a thermally conductive housing or athermoelectric controller. In some embodiments, the optical fibers canbe oriented to direct light to the flow cell without the use of lensesor other optical elements. Other variations are also possible.Similarly, in any method or process disclosed herein, steps oroperations can be add, removed, and/or rearranged.

Reference throughout this specification to “some embodiments,” “certainembodiments,” or “an embodiment” means that a particular feature,structure or characteristic described in connection with the embodimentis included in at least some embodiments. Thus, appearances of thephrases “in some embodiments” or “in an embodiment” in various placesthroughout this specification are not necessarily all referring to thesame embodiment and may refer to one or more of the same or differentembodiments. Furthermore, the particular features, structures orcharacteristics may be combined in any suitable manner, as would beapparent to one of ordinary skill in the art from this disclosure, inone or more embodiments.

As used in this application, the terms “comprising,” “including,”“having,” and the like are synonymous and are used inclusively, in anopen-ended fashion, and do not exclude additional elements, features,acts, operations, and so forth. Also, the term “or” is used in itsinclusive sense (and not in its exclusive sense) so that when used, forexample, to connect a list of elements, the term “or” means one, some,or all of the elements in the list.

Similarly, it should be appreciated that in the above description ofembodiments, various features are sometimes grouped together in a singleembodiment, figure, or description thereof for the purpose ofstreamlining the disclosure and aiding in the understanding of one ormore of the various inventive aspects. This method of disclosure,however, is not to be interpreted as reflecting an intention that anyclaim require more features than are expressly recited in that claim.Rather, inventive aspects lie in a combination of fewer than allfeatures of any single foregoing disclosed embodiment.

Although the inventions presented herein have been disclosed in thecontext of certain preferred embodiments and examples, it will beunderstood by those skilled in the art that the inventions extend beyondthe specifically disclosed embodiments to other alternative embodimentsand/or uses of the inventions and obvious modifications and equivalentsthereof. Thus, it is intended that the scope of the inventions hereindisclosed should not be limited by the particular embodiments describedabove.

What is claimed is:
 1. A multi-laser system, comprising: a laserconfigured to output a laser beam; and a beam adjusting systemconfigured to adjust an angular position of the laser beam and directthe adjusted laser beam toward a target object, the beam adjustingsystem comprising at least one meniscus shaped optical element having afirst surface and a second opposite surface, wherein said meniscusshaped optical element is adjustable to adjust the angular position ofthe laser beam, and wherein the target object comprises a flow cell. 2.The system of claim 1, wherein the first and second surfaces comprise afirst curved surface and a second curved surface opposite the firstcurved surface.
 3. The system of claim 2, wherein the first surface isconvex and the second surface is concave, and wherein the convex surfacereceives the laser beam prior to the concave surface.
 4. The system ofclaim 1, wherein the first and the second surface of the meniscus shapedoptical element are intersected by an optical axis.
 5. The system ofclaim 4, wherein the beam adjusting system comprises a mechanical systemconfigured to rotate the meniscus shaped optical element about two axesthat are orthogonal to the optical axis.
 6. The system of claim 5,wherein the two axes are orthogonal to each other.
 7. The system ofclaim 4, wherein the beam adjusting system comprises a mechanical systemconfigured to move the meniscus shaped optical element along an axisorthogonal to the optical axis.
 8. The system of claim 1, wherein themeniscus shaped optical element has less than about 1 dioptres opticalpower.
 9. The system of claim 1, wherein the laser beam is collimated atthe target object.
 10. A multi-laser system, comprising: a laserconfigured to output a laser beam; and a beam adjusting systemconfigured to adjust an angular position of the laser beam and directthe adjusted laser beam toward a target object, the beam adjustingsystem comprising at least one meniscus shaped optical element having afirst surface and a second opposite surface, wherein said meniscusshaped optical element is adjustable to adjust the angular position ofthe laser beam, wherein the first and the second surface of the meniscusshaped optical element are intersected by an optical axis, and whereinthe beam adjusting system comprises a mechanical system configured torotate the meniscus shaped optical element about two axes that areorthogonal to the optical axis.
 11. The system of claim 10, wherein thefirst and second surfaces comprise a first curved surface and a secondcurved surface opposite the first curved surface.
 12. The system ofclaim 11, wherein the first surface is convex and the second surface isconcave, and wherein the convex surface receives the laser beam prior tothe concave surface.
 13. The system of claim 10, wherein the two axesare orthogonal to each other.
 14. The system of claim 10, wherein themeniscus shaped optical element has less than about 1 dioptres opticalpower.
 15. The system of claim 10, wherein the target object comprises aflow cell.
 16. The system of claim 10, wherein the laser beam iscollimated at the target object.
 17. A multi-laser system, comprising: alaser configured to output a laser beam; and a beam adjusting systemconfigured to adjust an angular position of the laser beam and directthe adjusted laser beam toward a target object, the beam adjustingsystem comprising at least one meniscus shaped optical element having afirst surface and a second opposite surface, wherein said meniscusshaped optical element is adjustable to adjust the angular position ofthe laser beam, wherein the first and the second surface of the meniscusshaped optical element are intersected by an optical axis, and whereinthe beam adjusting system comprises a mechanical system configured tomove the meniscus shaped optical element along an axis orthogonal to theoptical axis.
 18. The system of claim 17, wherein the first and secondsurfaces comprise a first curved surface and a second curved surfaceopposite the first curved surface.
 19. The system of claim 18, whereinthe first surface is convex and the second surface is concave, andwherein the convex surface receives the laser beam prior to the concavesurface.
 20. The system of claim 17, wherein the meniscus shaped opticalelement has less than about 1 dioptres optical power.
 21. The system ofclaim 17, wherein the target object comprises a flow cell.
 22. Thesystem of claim 17, wherein the laser beam is collimated at the targetobject.
 23. The system of claim 2, wherein the first surface is concaveand the second surface is convex, and wherein the concave surfacereceives the laser beam prior to the convex surface.
 24. The system ofclaim 2, wherein a radius of curvature of the first curved surface issubstantially equal to the radius of curvature of the second curvedsurface.
 25. The system of claim 4, wherein the beam adjusting systemcomprises a mechanical system configured to rotate the meniscus shapedoptical element about an axis that is orthogonal to the optical axis.26. The system of claim 25, wherein the axis about which the meniscusshaped optical element is rotated is the horizontal axis or the verticalaxis.
 27. The system of claim 6, wherein one of the two axes ishorizontal and one of the two axes is vertical.
 28. The system of claim4, wherein the axis along which the meniscus shaped optical element ismoved is the horizontal axis or the vertical axis.
 29. The system ofclaim 4, wherein the beam adjusting system comprises a mechanical systemconfigured to move the meniscus shaped optical element along two axesthat are orthogonal to the optical axis.
 30. The system of claim 29,wherein the two axes are orthogonal to each other.
 31. The system ofclaim 30, wherein one of the two axes is horizontal and one of the twoaxes is vertical.
 32. The system of claim 1, wherein the meniscus shapedoptical element has a low optical power.
 33. The system of claim 1,wherein the meniscus shaped optical element has less than about 0.5dioptres optical power.
 34. The system of claim 1, wherein the meniscusshaped optical element has less than about 0.25 dioptres optical power.35. The system of claim 1, wherein the meniscus shaped optical elementhas negligible optical power.
 36. The system of claim 1, wherein theradii of curvature and thickness of the meniscus shaped optical elementcan be optimized for the angular beam adjustment required.
 37. Thesystem of claim 1, comprising a plurality of lasers configured to outputa plurality of respective laser beams.